The correlation of cathodic peak potentials of vitamin K(3) derivatives and their calculated electron affinities. The role of hydrogen bonding and conformational changes.

PubMed

Nasiri, Hamid Reza; Panisch, Robin; Madej, M Gregor; Bats, Jan W; Lancaster, C Roy D; Schwalbe, Harald

2009-06-01

2-methyl-1,4-naphtoquinone 1 (vitamin K(3), menadione) derivatives with different substituents at the 3-position were synthesized to tune their electrochemical properties. The thermodynamic midpoint potential (E(1/2)) of the naphthoquinone derivatives yielding a semi radical naphthoquinone anion were measured by cyclic voltammetry in the aprotic solvent dimethoxyethane (DME). Using quantum chemical methods, a clear correlation was found between the thermodynamic midpoint potentials and the calculated electron affinities (E(A)). Comparison of calculated and experimental values allowed delineation of additional factors such as the conformational dependence of quinone substituents and hydrogen bonding which can influence the electron affinities (E(A)) of the quinone. This information can be used as a model to gain insight into enzyme-cofactor interactions, particularly for enzyme quinone binding modes and the electrochemical adjustment of the quinone motif.

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.

CHARGE-TRANSFER ASSOCIATION AND PARAMAGNETISM OF SOME ORGANIC SYSTEMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eastman, J W

When p-xylene was combined with chloranil in n-heptane, charge-transfer optical absorption was observed. The magnitude of this absorption was used to calculate an equilibrium constant for the formation of a donor-acceptor complex containing one p-xylene was combined with carbon tetrabromide and with carbon tetrachloride in n-heptane, no charge-transfer absorption was observed. Reactions of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) with chloranil (pQCl/ sub 4/) were observed in ethylene dichloride and acetonitrile. In both solvents adduct formation occurred initially, as observed by its charge-transfer absorption. In acetonitrile time-dependent electron spin resonance (ESR) absorption was observed, and it was identified with the positive and negative radicalmore » ions of TMPD and pQCl/sub 4/, respectively. In this case a completely ionized electron transfer had occurred. Chloranil and other quinones were found to react with N,N-dimethylaniline forming a crystal violet salt. The diamagnetic donor-acceptor complexes and also semiquinone radicals are intermediates which were observed. Some physical measurements of the kinetics of this reaction are described and correlated. When fluoranil was allowed to react with dimethylaniline, the hyperfine splitting by the fluorine atoms of the fluoranil radical was not resolved. Characteristics of the ESR absorption by this radical in dimethylaniline are discussed in terms of an electron transfer between the semiquinone and quinone, and between the semiquinone and hydroquinone ion. Paramagnetism was discovered in hydrocarbon-quinone solids. ESR absorption was assigned to imperfections in the solid which was normally diamagnetic. The preparation of these solids and some of their physical characteristics are described. (auth)« less

Photoinduced electron transfer interaction of anthraquinones with aniline quenchers: Influence of methyl substitution in aniline donors

NASA Astrophysics Data System (ADS)

Sivakumar, V.; Ponnamma, Deepalekshmi; Hussein, Yasser H. A.

2017-02-01

Photoinduced electron transfer between triplet state of 9,10-anthraquinone (AQ) and its two derivatives: 2-chloro-9,10-anthraquinone (CAQ) and sodium anthraquinone-2-sulfonate (AQS) and ground state aniline (AN) and its dimethyl substitutions: 2,3-dimethylaniline (2,3-DMA), 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA) and N,N-dimethylaniline (N,N-DMA) is studied using nanosecond laser flash photolysis at room temperature. Detection of radical bands of quinone anions and aniline cations along with their formation and/or decay kinetics are used to confirm the electron transfer (ET) process. In MeCN medium, AN quenches the triplet state of CAQ (CAQT) but not the triplets AQT or AQST. However in aqueous medium, AN quenches AQST and forms radical ion pair. All the DMAs can react through ET with all the triplet quinones at different degrees of efficiency in MeCN medium. Noticeably, the ring substituted DMAs are less efficient in electron donation to AQT or AQST while the N,N-DMA shows high efficiency in donating electron to all triplet quinones in MeCN medium. Charge distribution of donor molecules, in MeCN medium is calculated using density functional theory (DFT), and shows an enhancement of electron density of the ring of N,N-DMA, making it an ideal electron donor for ET studies compared to other DMAs. This systematic selection and usage of anilines with electrochemically tunable quinones can be viewed as a working model of donor-acceptor system that can be utilized in photoinduced ET applications.

Synthesis of Resveratrol Tetramers via a Stereoconvergent Radical Equilibrium

PubMed Central

Keylor, Mitchell H.; Matsuura, Bryan S.; Griesser, Markus; Chauvin, Jean-Philippe R.; Harding, Ryan A.; Kirillova, Mariia S.; Zhu, Xu; Fischer, Oliver J.; Pratt, Derek A.; Stephenson, Corey R. J.

2017-01-01

Persistent free radicals have become indispensable in the synthesis of organic materials by living radical polymerization. However, examples of their use in the synthesis of small molecules are rare. Herein, we report the application of persistent radical and quinone methide intermediates to the synthesis of the resveratrol tetramers nepalensinol B and vateriaphenol C. The spontaneous cleavage and reconstitution of exceptionally weak carbon-carbon bonds has enabled a stereoconvergent oxidative dimerization of racemic materials in a transformation that likely coincides with the biogenesis of these natural products. The efficient synthesis of higher-order oligomers of resveratrol will facilitate the biological studies necessary to elucidate their mechanism(s) of action. PMID:27940867

Mechanism of pyrogallol red oxidation induced by free radicals and reactive oxidant species. A kinetic and spectroelectrochemistry study.

PubMed

Atala, E; Velásquez, G; Vergara, C; Mardones, C; Reyes, J; Tapia, R A; Quina, F; Mendes, M A; Speisky, H; Lissi, E; Ureta-Zañartu, M S; Aspée, A; López-Alarcón, C

2013-05-02

Pyrogallol red (PGR) presents high reactivity toward reactive (radical and nonradical) species (RS). This property of PGR, together with its characteristic spectroscopic absorption in the visible region, has allowed developing methodologies aimed at evaluating the antioxidant capacity of foods, beverages, and human fluids. These methods are based on the evaluation of the consumption of PGR induced by RS and its inhibition by antioxidants. However, at present, there are no reports regarding the degradation mechanism of PGR, limiting the extrapolation to how antioxidants behave in different systems comprising different RS. In the present study, we evaluate the kinetics of PGR consumption promoted by different RS (peroxyl radicals, peroxynitrite, nitrogen dioxide, and hypochlorite) using spectroscopic techniques and detection of product by HPLC mass spectrometry. The same pattern of oxidation and spectroscopic properties of the products is observed, independently of the RS employed. Mass analysis indicates the formation of only one product identified as a quinone derivative, excluding the formation of peroxides or hydroperoxides and/or chlorinated compounds, in agreement with FOX's assays and oxygen consumption experiments. Cyclic voltammetry, carried out at different pH's, shows an irreversible oxidation of PGR, indicating the initial formation of a phenoxy radical and a second charge transfer reaction generating an ortho-quinone derivative. Spectroelectrochemical oxidation of PGR shows oxidation products with identical UV-visible absorption properties to those observed in RS-induced oxidation.

Multicomponent kinetic analysis and theoretical studies on the phenolic intermediates in the oxidation of eugenol and isoeugenol catalyzed by laccase.

PubMed

Qi, Yan-Bing; Wang, Xiao-Lei; Shi, Ting; Liu, Shuchang; Xu, Zhen-Hao; Li, Xiqing; Shi, Xuling; Xu, Ping; Zhao, Yi-Lei

2015-11-28

Laccase catalyzes the oxidation of natural phenols and thereby is believed to initialize reactions in lignification and delignification. Numerous phenolic mediators have also been applied in laccase-mediator systems. However, reaction details after the primary O-H rupture of phenols remain obscure. In this work two types of isomeric phenols, EUG (eugenol) and ISO (trans-/cis-isoeugenol), were used as chemical probes to explore the enzymatic reaction pathways, with the combined methods of time-resolved UV-Vis absorption spectra, MCR-ALS, HPLC-MS, and quantum mechanical (QM) calculations. It has been found that the EUG-consuming rate is linear to its concentration, while the ISO not. Besides, an o-methoxy quinone methide intermediate, (E/Z)-4-allylidene-2-methoxycyclohexa-2,5-dienone, was evidenced in the case of EUG with the UV-Vis measurement, mass spectra and TD-DFT calculations; in contrast, an ISO-generating phenoxyl radical, a (E/Z)-2-methoxy-4-(prop-1-en-1-yl) phenoxyl radical, was identified in the case of ISO. Furthermore, QM calculations indicated that the EUG-generating phenoxyl radical (an O-centered radical) can easily transform into an allylic radical (a C-centered radical) by hydrogen atom transfer (HAT) with a calculated activation enthalpy of 5.3 kcal mol(-1) and then be fast oxidized to the observed eugenol quinone methide, rather than an O-radical alkene addition with barriers above 12.8 kcal mol(-1). In contrast, the ISO-generating phenoxyl radical directly undergoes a radical coupling (RC) process, with a barrier of 4.8 kcal mol(-1), while the HAT isomerization between O- and C-centered radicals has a higher reaction barrier of 8.0 kcal mol(-1). The electronic conjugation of the benzyl-type radical and the aromatic allylic radical leads to differentiation of the two pathways. These results imply that competitive reaction pathways exist for the nascent reactive intermediates generated in the laccase-catalyzed oxidation of natural phenols, which is important for understanding the lignin polymerization and may shed some light on the development of efficient laccase-mediator systems.

Photoinduced electron transfer interaction of anthraquinones with aniline quenchers: Influence of methyl substitution in aniline donors.

PubMed

Sivakumar, V; Ponnamma, Deepalekshmi; Hussein, Yasser H A

2017-02-15

Photoinduced electron transfer between triplet state of 9,10-anthraquinone (AQ) and its two derivatives: 2-chloro-9,10-anthraquinone (CAQ) and sodium anthraquinone-2-sulfonate (AQS) and ground state aniline (AN) and its dimethyl substitutions: 2,3-dimethylaniline (2,3-DMA), 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA) and N,N-dimethylaniline (N,N-DMA) is studied using nanosecond laser flash photolysis at room temperature. Detection of radical bands of quinone anions and aniline cations along with their formation and/or decay kinetics are used to confirm the electron transfer (ET) process. In MeCN medium, AN quenches the triplet state of CAQ (CAQ T ) but not the triplets AQ T or AQS T . However in aqueous medium, AN quenches AQS T and forms radical ion pair. All the DMAs can react through ET with all the triplet quinones at different degrees of efficiency in MeCN medium. Noticeably, the ring substituted DMAs are less efficient in electron donation to AQ T or AQS T while the N,N-DMA shows high efficiency in donating electron to all triplet quinones in MeCN medium. Charge distribution of donor molecules, in MeCN medium is calculated using density functional theory (DFT), and shows an enhancement of electron density of the ring of N,N-DMA, making it an ideal electron donor for ET studies compared to other DMAs. This systematic selection and usage of anilines with electrochemically tunable quinones can be viewed as a working model of donor-acceptor system that can be utilized in photoinduced ET applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrochemical oxidation of wine polyphenols in the presence of sulfur dioxide.

PubMed

Makhotkina, Olga; Kilmartin, Paul A

2013-06-12

Electrochemical oxidation of three representative wine polyphenols (catechin, caffeic acid, and quercetin) in the presence of sulfur dioxide in a model wine solution (pH = 3.3) was investigated. The oxidation was undertaken using chronoamperometry at a rotating glassy carbon rod electrode, and the reaction products were characterized by HPLC-MS. The mechanism of electrochemical oxidation of polyphenols in the presence of sulfur dioxide was proposed to be an ECEC mechanism. The polyphenols first underwent a one-electron oxidation to a semiquinone radical, which can be reduced back to the original polyphenol by sulfur dioxide, or further oxidized to the quinone form. In the cases of caffeic acid and catechin, the quinone combined with sulfur dioxide and produced new derivatives. The quercetin quinone underwent further chemical transformations, producing several new compounds. The proposed mechanisms were confirmed by digital simulation of cyclic voltammograms.

Artificial photosynthesis using chlorophyll based carotenoid quinone triads: A brief synopsis of research progress as of 31 December 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gust, D.; Moore, T.A.

1986-12-31

The design, synthesis and study of a series of carotenoid-chlorophyll-quinone triad molecules which mimic some of the basic photochemistry and photophysics of natural photosynthesis is sought. The first members of this series have now been prepared, and have been found to mimic photosynthetic charge separation, carotenoid antenna function, and carotenoid photoprotection from singlet oxygen damage. Although the triad molecules mimic the general principle of multistep electron transfer which is found in natural photosynthesis, the details of photosynthetic electron transfer differ in the triads, in that the first electron transfer step involves electron donation from the excited state donor, followed bymore » reduction of the resulting donor radical cation by the carotenoid. In photosynthesis, the electron is moved through several acceptors before the chlorophyll radical cation is reduced. Therefore, our recent work has concentrated on the design and synthesis of new model systems which better mimic certain aspects of natural photosynthesis.« less

Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells.

PubMed

Moridani, Majid Y

2006-11-18

In the current work we investigated for the first time the biochemical basis of 4-hydroxyanisole (4-HA) induced toxicity in B16-F0 melanoma cells. It was found that dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased 4-HA induced toxicity towards B16-F0 cells whereas dithiothreitol, a thiol containing agent, and ascorbic acid (AA), a reducing agent, largely prevented 4-HA toxicity. TEMPOL and pyrogallol, free radical scavengers, did not significantly prevent 4-HA toxicity towards B16-F0 cells. GSH>AA>NADH prevented the o-quinone formation when 4-HA was metabolized by tyrosinase/O(2). 4-HA metabolism by horseradish peroxidase/H(2)O(2) was prevented more effectively by AA than NADH>GSH. We therefore concluded that quinone formation was the major pathway for 4-HA induced toxicity in B16-F0 melanoma cells whereas free radical formation played a negligible role in the 4-HA induced toxicity.

In vitro activity of almond skin polyphenols for scavenging free radicals and inducing quinone reductase.

PubMed

Chen, C-Y Oliver; Blumberg, Jeffrey B

2008-06-25

Observational studies and clinical trials suggest nut intake, including almonds, is associated with an enhancement in antioxidant defense and a reduction in the risk of cancer and cardiovascular disease. Almond skins are rich in polyphenols (ASP) that may contribute to these putative benefits. To assess their potential mechanisms of action, we tested the in vitro effect of ASP extracted with methanol (M) or a gastrointestinal juice mimic (GI) alone or in combination with vitamins C (VC) or E (VE) (1-10 micromol/L) on scavenging free radicals and inducing quinone reductase (QR). Flavonoid profiles from ASP-M and -GI extracts were different from one another. ASP-GI was more potent in scavenging HOCl and ONOO (-) radicals than ASP-M. In contrast, ASP-M increased and ASP-GI decreased QR activity in Hepa1c1c7 cells. Adding VC or VE to ASP produced a combination- and dose-dependent action on radical scavenging and QR induction. In comparison to their independent actions, ASP-M plus VC were less potent in scavenging DPPH, HOCl, ONOO (-), and O 2 (-) (*). However, the interaction between ASP-GI plus VC promoted their radical scavenging activity. Combining ASP-M plus VC resulted in a synergistic interaction, inducing QR activity, but ASP-GI plus VC had an antagonistic effect. On the basis of their total phenolic content, the measures of total antioxidant activity of ASP-M and -GI were comparable. Thus, in vitro, ASP act as antioxidants and induce QR activity, but these actions are dependent upon their dose, method of extraction, and interaction with antioxidant vitamins.

In vitro activity of almond skin polyphenols for scavenging free radicals and inducing quinone reductase

USDA-ARS?s Scientific Manuscript database

Observational studies and clinical trials suggest nut intake, including almonds, is associated with an enhancement in antioxidant defense and a reduction in risk of cancer and cardiovascular disease. Almond skins are rich in polyphenols (ASP) that may contribute to these putative benefits. To assess...

The Quinone Based Antitumor Agent Sepantronium Bromide (YM155) Causes Oxygen Independent Redox Activated Oxidative DNA Damage.

PubMed

Wani, Tasaduq Hussain; Surendran, Sreeraj; Jana, Anal; Chakrabarty, Anindita; Chowdhury, Goutam

2018-06-13

Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Knowing the mechanism of action of an anticancer drug is necessary to formulate a rational drug combination and select a cancer type for achieving maximum clinical efficacy. Using cell-based assays we showed that YM155 cause extensive DNA cleavage and reactive oxygen species generation. DNA cleavage by YM155 was found to be inhibited by radical scavengers and desferal. The reducing agent DTT and the cellular reducing system xanthine/xanthine oxidase were found to reductively activate YM155 and cause DNA cleavage. Unlike quinones, DNA cleavage by YM155 occurs in the presence of catalase and under hypoxic conditions indicating that hydrogen peroxide and oxygen is not necessary. Although YM155 is a quinone, it does not follow a typical quinone mechanism. Consistent with these observations a mechanism has been proposed that suggests that YM155 can cause oxidative DNA cleavage upon two electron reductive activation.

Further insights into the oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,6-dihydroxytryptamine.

PubMed

Singh, S; Dryhurst, G

1990-11-01

The neurodegenerative properties of the serotonergic neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) are widely believed to result from its autoxidation in the central nervous system. The autoxidation chemistry of 5,6-DHT has been studied in aqueous solution at pH 7.2. The reaction is initiated by direct oxidation of the indolamine by molecular oxygen with resultant formation of the corresponding o-quinone 1 and H2O2. A rapid nucleophilic attack by 5,6-DHT on 1 leads to 2,7'-bis(5,6-dihydroxytryptamine) (6) which is more rapidly autoxidized than 5,6-DHT to give the corresponding diquinone 7 along with 2 mol of H2O2. The accumulation of 6 in the reaction solution during the autoxidation of 5,6-DHT despite its more rapid autoxidation indicates that diquinone 7 chemically oxidizes 5,6-DHT (2 mol) to quinone 1 so that an autocatalytic cycle is established. The H2O2 formed as a byproduct of these autoxidation reactions can undergo Fenton chemistry catalyzed by trace transition metal ion contaminants with resultant formation of the hydroxyl radical, HO., which directly oxidizes 5,6-DHT to a radical intermediate (9a/9b). This radical is directly attacked by O2 to yield quinone 1 and superoxide radical anion, O2.-, which further facilitates Fenton chemistry by reducing, inter alia, Fe3+ to Fe2+. A minor side reaction of 1 with water leads to formation of at least two trihydroxytryptamines. Diquinone 7 ultimately reacts with 6, 5,6-DHT, and perhaps trihydroxytryptamines, leading via a sequence of coupling and oxidation reactions to a black indolic melanin polymer. Enzymes such as tyrosinase, ceruloplasmin, and peroxidase and rat brain mitochondria catalyze the oxidation of 5,6-DHT to form dimer 7 and, ultimately, indolic melanin. The role of the autoxidation and the enzyme-mediated and mitochondria-promoted oxidations of 5,6-DHT in expressing the neurodegenerative properties of the indolamine are discussed.

USING STRUCTURAL EFFECTS ON THE ORGANIZATION OF THE CYTOSKELETON OF RAINBOW TROUT HEPATOCYTES TO SORT PATHWAYS OF REACTIVE TOXICITY

EPA Science Inventory

Quinones have been shown to be more acutely toxic to aquatic organisms than chemicals that are not capable of either direct interaction with cellular nucleophiles or potentially metabolized free radicals. For the development of accurate QSAR models, in vitro toxicity assays are n...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pegan, Scott D.; Sturdy, Megan; Ferry, Gilles

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 humanmore » 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.« less

Toward Improved Catholyte Materials for Redox Flow Batteries: What Controls Chemical Stability of Persistent Radical Cations?

DOE PAGES

Zhang, Jingjing; Shkrob, Ilya A.; Assary, Rajeev S.; ...

2017-10-06

We report catholyte materials are used to store positive charge in energized fluids circulating through redox flow batteries (RFBs) for electric grid and vehicle applications. Energy-rich radical cations (RCs) are being considered for use as catholyte materials, but to be practically relevant, these RCs (that are typically unstable, reactive species) need to have long lifetimes in liquid electrolytes under the ambient conditions. Only few families of such energetic RCs possess stabilities that are suitable for their use in RFBs; currently, the derivatives of 1,4- dialkoxybenzene look the most promising. In this study, we examine factors that define the chemical andmore » electrochemical stabilities for RCs in this family. To this end, we engineered rigid bis-annulated molecules that by design avoid the two main degradation pathways for such RCs, viz. their deprotonation and radical addition. The decay of the resulting RCs are due to the single remaining reaction: O-dealkylation. We establish the mechanism for this reaction and examine factors controlling its rate. In particular, we demonstrate that this reaction is initiated by the nucleophile attack of the counter anion on the RC partner. The reaction proceeds through the formation of the aroxyl radicals whose secondary reactions yield the corresponding quinones. The O-dealkylation accelerates considerably when the corresponding quinone has poor solubility in the electrolyte, and the rate depends strongly on the solvent polarity. Finally, our mechanistic insights suggest new ways of improving the RC catholytes through molecular engineering and electrolyte optimization.« less

Toward Improved Catholyte Materials for Redox Flow Batteries: What Controls Chemical Stability of Persistent Radical Cations?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jingjing; Shkrob, Ilya A.; Assary, Rajeev S.

We report catholyte materials are used to store positive charge in energized fluids circulating through redox flow batteries (RFBs) for electric grid and vehicle applications. Energy-rich radical cations (RCs) are being considered for use as catholyte materials, but to be practically relevant, these RCs (that are typically unstable, reactive species) need to have long lifetimes in liquid electrolytes under the ambient conditions. Only few families of such energetic RCs possess stabilities that are suitable for their use in RFBs; currently, the derivatives of 1,4- dialkoxybenzene look the most promising. In this study, we examine factors that define the chemical andmore » electrochemical stabilities for RCs in this family. To this end, we engineered rigid bis-annulated molecules that by design avoid the two main degradation pathways for such RCs, viz. their deprotonation and radical addition. The decay of the resulting RCs are due to the single remaining reaction: O-dealkylation. We establish the mechanism for this reaction and examine factors controlling its rate. In particular, we demonstrate that this reaction is initiated by the nucleophile attack of the counter anion on the RC partner. The reaction proceeds through the formation of the aroxyl radicals whose secondary reactions yield the corresponding quinones. The O-dealkylation accelerates considerably when the corresponding quinone has poor solubility in the electrolyte, and the rate depends strongly on the solvent polarity. Finally, our mechanistic insights suggest new ways of improving the RC catholytes through molecular engineering and electrolyte optimization.« less

Radiolysis of paracetamol in dilute aqueous solution

NASA Astrophysics Data System (ADS)

Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

2012-09-01

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O2 is c.a. 10%. The efficiency is 2-3 times higher in the presence of O2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily.

Tyrosine radicals are involved in the photosynthetic oxygen-evolving system.

PubMed Central

Barry, B A; Babcock, G T

1987-01-01

In addition to the reaction-center chlorophyll, at least two other organic cofactors are involved in the photosynthetic oxygen-evolution process. One of these cofactors, called "Z," transfers electrons from the site of water oxidation to the reaction center of photosystem II. The other species, "D," has an uncertain function but gives rise to the stable EPR signal known as signal II. Z+. and D+. have identical EPR spectra and are generally assumed to arise from species with the same chemical structure. Results from a variety of experiments have suggested that Z and D are plastoquinones or plastoquinone derivatives. In general, however, the evidence to support this assignment is indirect. To address this situation, we have developed more direct methods to assign the structure of the Z+./D+. radicals. By selective in vivo deuteration of the methyl groups of plastoquinone in cyanobacteria, we show that hyperfine couplings from the methyl protons cannot be responsible for the partially resolved structure seen in the D+. EPR spectrum. That is, we verify by extraction and mass spectrometry that quinones are labeled in algae fed deuterated methionine, but no change is observed in the line shape of signal II. Considering the spectral properties of the D+. radical, a tyrosine origin is a reasonable alternative. In a second series of experiments, we have found that deuteration of tyrosine does indeed narrow the D+. signal. Extraction and mass spectral analysis of the quinones in these cultures show that they are not labeled by tyrosine. These results eliminate a plastoquinone origin for D+.; we conclude instead that D+., and most likely Z+., are tyrosine radicals. PMID:3313386

Reducing capacities and redox potentials of humic substances extracted from sewage sludge.

PubMed

Yang, Zhen; Du, Mengchan; Jiang, Jie

2016-02-01

Humic substances (HS) are redox active organic materials that can be extracted from sewage sludge generated in wastewater treatment processes. Due to the poor understanding of reducing capacity, redox potentials and redox active functional groups of HS in sewage sludge, the potential contribution of sludge HS in transformation of wastewater contaminants is unclear. In the present study, the number of electrons donated or accepted by sewage sludge HS were quantified before and after reduction by iron compounds that possess different redox potentials and defined as the reducing capacity of the sewage sludge. In contrast to previous studies of soil and commercial humic acids (HA), reduced sludge HA showed a lower reducing capacity than that of native HA, which implies formation of semiquinone radicals since the semiquinone radical/hydroquinone pair has a much higher redox potential than the quinone/hydroquinone pair. It is novel that reducing capacities of sludge HA were determined in the redox potential range from -314 to 430 mV. The formation of semiquinone radicals formed during the reduction of quinone moieties in sludge HA is shown by three-dimensional excitation/emission matrix fluorescence spectroscopies information, increasing fluorescence intensities and blue-shifting of the excitation/emission peak of reduced sludge HA. Knowledge of sludge HS redox potentials and corresponding reducing capacities makes it possible to predict the transformation of redox active pollutants and facilitate manipulation and optimization of sludge loading wastewater treatment processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

EPR studies of the vitamin K 1 semiquinone radical anion. Comparison to the electron acceptor A 1 in green plant photosystem I

NASA Astrophysics Data System (ADS)

Thurnauer, Marion C.; Brown, James W.; Gast, P.; Feezel, Laura L.

Suggestions that the electron acceptor, A 1, in Photosystem I is a quinone have come from both optical and epr experiments. Vitamin K 1 (phylloquinone) is present in the PSI complex with a stoichiometry of two molecules per reaction center. In order to determine if A 1 can be identified with vitamin K 1, X-band and Q-band epr properties of the vitamin K 1 radical anion in frozen alcohol solutions are examined. The results are compared to the epr properties that have been observed for the reduced A 1 acceptor in vivo. The g-values obtained for the vitamin K 1 radical anion are consistent with identifying A 1 with vitamin K 1.

Oxygen activation at the plasma membrane: relation between superoxide and hydroxyl radical production by isolated membranes.

PubMed

Heyno, Eiri; Mary, Véronique; Schopfer, Peter; Krieger-Liszkay, Anja

2011-07-01

Production of reactive oxygen species (hydroxyl radicals, superoxide radicals and hydrogen peroxide) was studied using EPR spin-trapping techniques and specific dyes in isolated plasma membranes from the growing and the non-growing zones of hypocotyls and roots of etiolated soybean seedlings as well as coleoptiles and roots of etiolated maize seedlings. NAD(P)H mediated the production of superoxide in all plasma membrane samples. Hydroxyl radicals were only produced by the membranes of the hypocotyl growing zone when a Fenton catalyst (FeEDTA) was present. By contrast, in membranes from other parts of the seedlings a low rate of spontaneous hydroxyl radical formation was observed due to the presence of small amounts of tightly bound peroxidase. It is concluded that apoplastic hydroxyl radical generation depends fully, or for the most part, on peroxidase localized in the cell wall. In soybean plasma membranes from the growing zone of the hypocotyl pharmacological tests showed that the superoxide production could potentially be attributed to the action of at least two enzymes, an NADPH oxidase and, in the presence of menadione, a quinone reductase.

Regulatory interactions in the dimeric cytochrome bc(1) complex: the advantages of being a twin.

PubMed

Covian, Raul; Trumpower, Bernard L

2008-09-01

The dimeric cytochrome bc(1) complex catalyzes the oxidation-reduction of quinol and quinone at sites located in opposite sides of the membrane in which it resides. We review the kinetics of electron transfer and inhibitor binding that reveal functional interactions between the quinol oxidation site at center P and quinone reduction site at center N in opposite monomers in conjunction with electron equilibration between the cytochrome b subunits of the dimer. A model for the mechanism of the bc(1) complex has emerged from these studies in which binding of ligands that mimic semiquinone at center N regulates half-of-the-sites reactivity at center P and binding of ligands that mimic catalytically competent binding of ubiquinol at center P regulates half-of-the-sites reactivity at center N. An additional feature of this model is that inhibition of quinol oxidation at the quinone reduction site is avoided by allowing catalysis in only one monomer at a time, which maximizes the number of redox acceptor centers available in cytochrome b for electrons coming from quinol oxidation reactions at center P and minimizes the leakage of electrons that would result in the generation of damaging oxygen radicals.

DNA strand scission induced by adriamycin and aclacinomycin A.

PubMed

Someya, A; Tanaka, N

1979-08-01

The binding of adriamycin and aclacinomycin A with PM2 DNA, and the consequent cleavage of DNA have been demonstrated by agarose gel electrophoresis, using an ethidium bromide assay. Adriamycin was observed to induce a single strand scission of DNA in the presence of a reducing agent, but aclacinomycin A caused much less degree of DNA breaks. The DNA cleavage was enhanced by Cu2+ and Fe2+, but not significantly by Ni2+, Zn2+, Mg2+ and Ca2+, suggesting that reduction and auto-oxidation of the quinone moiety and H2O2 production participate in the DNA-cutting effect. The DNA degradation was dependent upon concentrations of the anthracyclines and CuCl2. The degree of DNA cleavage at 0.04 mM adriamycin was similar to that at 0.4 mM aclacinomycin A in the presence of 1 mM NADPH and 0.4 mM CuCl2. DNA was degraded to small fragments at 0.4 mM adriamycin and 0.2 mM CuCl2. The anthracycline-induced DNA cleavage was stimulated by H2O2, but partially inhibited by potassium iodide, superoxide dismutase, catalase and nitrogen gas atmosphere. The results suggested that both free radical of anthracycline quinones and hydroxyl radical directly react with DNA strands.

Free radical scavenging potency of quercetin catecholic colonic metabolites: Thermodynamics of 2H+/2e- processes.

PubMed

Amić, Ana; Lučić, Bono; Stepanić, Višnja; Marković, Zoran; Marković, Svetlana; Dimitrić Marković, Jasmina M; Amić, Dragan

2017-03-01

Reaction energetics of the double (2H + /2e - ), i.e., the first 1H + /1e - (catechol→ phenoxyl radical) and the second 1H + /1e - (phenoxyl radical→ quinone) free radical scavenging mechanisms of quercetin and its six colonic catecholic metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid, protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied using density functional theory, with the aim to estimate the antiradical potency of these molecules. We found that second hydrogen atom transfer (HAT) and second sequential proton loss electron transfer (SPLET) mechanisms are less energy demanding than the first ones indicating 2H + /2e - processes as inherent to catechol moiety. The Gibbs free energy change for reactions of inactivation of selected free radicals indicate that catecholic colonic metabolites constitute an efficient group of more potent scavengers than quercetin itself, able to deactivate various free radicals, under different biological conditions. They could be responsible for the health benefits associated with regular intake of flavonoid-rich diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

BENZO[A]PYRENE-7,8-QUINONE FORMS COVALENT-DNA ADDUCTS IN VITRO BUT NONE WERE DETECTED IN THE LUNGS OR LIVERS OF STRAIN A/J MICE IN VIVO

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of B[a]P-7,8-dio1-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from radical cati...

Riboflavin Is an Active Redox Cofactor in the Na+-pumping NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

PubMed Central

Juárez, Oscar; Nilges, Mark J.; Gillespie, Portia; Cotton, Jennifer; Barquera, Blanca

2008-01-01

Here we present new evidence that riboflavin is present as one of four flavins in Na+-NQR. In particular, we present conclusive evidence that the source of the neutral radical is not one of the FMNs and that riboflavin is the center that gives rise to the neutral flavosemiquinone. The riboflavin is a bona fide redox cofactor and is likely to be the last redox carrier of the enzyme, from which electrons are donated to quinone. We have constructed a double mutant that lacks both covalently bound FMN cofactors (NqrB-T236Y/NqrC-T225Y) and have studied this mutant together with the two single mutants (NqrB-T236Y and NqrC-T225Y) and a mutant that lacks the noncovalently bound FAD in NqrF (NqrF-S246A). The double mutant contains riboflavin and FAD in a 0.6:1 ratio, as the only flavins in the enzyme; noncovalently bound flavins were detected. In the oxidized form, the double mutant exhibits an EPR signal consistent with a neutral flavosemiquinone radical, which is abolished on reduction of the enzyme. The same radical can be observed in the FAD deletion mutant. Furthermore, when the oxidized enzyme reacts with ubiquinol (the reduced form of the usual electron acceptor) in a process that reverses the physiological direction of the electron flow, a single kinetic phase is observed. The kinetic difference spectrum of this process is consistent with one-electron reduction of a neutral flavosemiquinone. The presence of riboflavin in the role of a redox cofactor is thus far unique to Na+-NQR. PMID:18832377

Photoinduced electron transfer in fixed distance chlorophyll-quinone donor-acceptor molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wasielewski, M.R.; Johnson, D.G.; Svec, W.A.

1987-01-01

A series of fixed distance chlorophyll-quinone donor-acceptor molecules have been prepared. The donor consists of either methyl pyropheophorbide a or methyl pyrochlorophyllide a, while the acceptor is either benzoquinone or naphthoquinone. The acceptors are fused to a triptycene spacer group, which in turn is attached to the donors at their vinyl groups. Picosecond transient absorption measurements have been used to identify electron transfer from the lowest excited singlet state of the donor to the acceptor as the mechanism of fluorescence quenching in these molecules. The charge separation rate constants increase from 2 x 10/sup 10/ s/sup -1/ to 4 xmore » 10/sup 11/ s/sup -1/ as the free energy of charge separation increases, while the radical pair recombination rate constants decrease from 1.2 x 10/sup 11/ s/sup -1/ to 2 x 10/sup 9/ s/sup -1/ as the free energy of recombination increases. The resulting total reorganization energy lambda = 0.9 eV.« less

Molecular complexes of L-phenylalanine with substituted 1,4-benzoquinones in aqueous medium: Spectral and theoretical investigations

NASA Astrophysics Data System (ADS)

Ganesh, K.; El-Mossalamy, E. H.; Satheshkumar, A.; Balraj, C.; Elango, K. P.

2013-12-01

Various spectral techniques such as UV-Vis, FT-IR, and fluorescence have been employed to investigate the charge transfer interaction of L-phenylalanine (LPA) with substituted 1,4-benzoquinones (MQ1-4). Kinetic and thermodynamic properties of the complexes were determined in aqueous medium at physiological condition (pH = 7). The interaction of MQ1-4 with L-phenylalanine (LPA) was found to proceed through the formation of donor-acceptor complex, yielding a radical anion. The stoichiometry of the complexes was determined by Jobs continuous variation method and was found to be 1:1 in all the cases. Fluorescence quenching studies showed that the interaction between the donor and the acceptors is spontaneous. The results indicated that the progressive replacement of chlorine atom (-I effect) by methoxy group (+M effect) in the quinone decreased the electron acceptor property of the quinone. The order of the experimentally measured association constant of these complexes was well supported by DFT/B3LYP calculations.

Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition: Experimental and Theoretical Studies.

PubMed

Escorihuela, Jorge; Das, Anita; Looijen, Wilhelmus J E; van Delft, Floris L; Aquino, Adelia J A; Lischka, Hans; Zuilhof, Han

2018-01-05

Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne-1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH ⧧ ) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH ⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3-8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.

Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition: Experimental and Theoretical Studies

PubMed Central

2017-01-01

Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne–1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH⧧) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3–8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches. PMID:29260879

Pathogenic Roles for Fungal Melanins

PubMed Central

Jacobson, Eric S.

2000-01-01

Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H2O2. Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning. PMID:11023965

Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton.

PubMed

Naman, C Benjamin; Li, Jie; Moser, Arvin; Hendrycks, Jeffery M; Benatrehina, P Annécie; Chai, Heebyung; Yuan, Chunhua; Keller, William J; Kinghorn, A Douglas

2015-06-19

Melanodiol 4″-O-protocatechuate (1) and melanodiol (2) represent novel flavonoid derivatives isolated from a botanical dietary supplement ingredient, dried black chokeberry (Aronia melanocarpa) fruit juice. These noncrystalline compounds possess an unprecedented fused pentacyclic core with two contiguous hemiketals. Due to having significant hydrogen deficiency indices, their structures were determined using computer-assisted structure elucidation software. The in vitro hydroxyl radical-scavenging and quinone reductase-inducing activity of each compound are reported, and a plausible biogenetic scheme is proposed.

Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton

PubMed Central

Naman, C. Benjamin; Li, Jie; Moser, Arvin; Hendrycks, Jeffery M.; Benatrehina, P. Annécie; Chai, Heebyung; Yuan, Chunhua; Keller, William J.; Kinghorn, A. Douglas

2015-01-01

Melanodiol 4″-O-protocatechuate (1) and melanodiol (2) represent novel flavonoid derivatives isolated from a botanical dietary supplement ingredient, dried black chokeberry (Aronia melanocarpa) fruit juice. These non-crystalline compounds possess an unprecedented fused pentacyclic core with two contiguous hemiketals. Due to having significant hydrogen deficiency indices, their structures were determined using computer-assisted structure elucidation software. The in vitro hydroxyl radical-scavenging and quinone reductase-inducing activity of each compound are reported, and a plausible biogenetic scheme is proposed PMID:26030740

Hydroquinone-Mediated Redox Cycling of Iron and Concomitant Oxidation of Hydroquinone in Oxic Waters under Acidic Conditions: Comparison with Iron-Natural Organic Matter Interactions.

PubMed

Jiang, Chao; Garg, Shikha; Waite, T David

2015-12-15

Interactions of 1,4-hydroquinone with soluble iron species over a pH range of 3-5 in the air-saturated and partially deoxygenated solution are examined here. Our results show that 1,4-hydroquinone reduces Fe(III) in acidic conditions, generating semiquinone radicals (Q(•-)) that can oxidize Fe(II) back to Fe(III). The oxidation rate of Fe(II) by Q(•-)increases with increase in pH due to the speciation change of Q(•-) with its deprotonated form (Q(•-)) oxidizing Fe(II) more rapidly than the protonated form (HQ(•)). Although the oxygenation of Fe(II) is negligible at pH < 5, O2 still plays an important role in iron redox transformation by rapidly oxidizing Q(•-) to form benzoquinone (Q). A kinetic model is developed to describe the transformation of quinone and iron under all experimental conditions. The results obtained here are compared with those obtained in our previous studies of iron-Suwannee River fulvic acid (SRFA) interactions in acidic solutions and support the hypothesis that hydroquinone moieties can reduce Fe(III) in natural waters. However, the semiquinone radicals generated in pure hydroquinone solution are rapidly oxidized by dioxygen, while the semiquinone radicals generated in SRFA solution are resistant to oxidation by dioxygen, with the result that steady-state semiquinone concentrations in SRFA solutions are 2-3 orders of magnitude greater than in solutions of 1,4-hydroquinone. As a result, semiquinone moieties in SRFA play a much more important role in iron redox transformations than is the case in solutions of simple quinones such as 1,4-hydroquinone. This difference in the steady-state concentration of semiquinone species has a dramatic effect on the cycling of iron between the +II and +III oxidation states, with iron turnover frequencies in solutions containing SRFA being 10-20 times higher than those observed in solutions of 1,4-hydroquinone.

Differential Cytochrome P450 2D Metabolism Alters Tafenoquine Pharmacokinetics

PubMed Central

Vuong, Chau; Xie, Lisa H.; Potter, Brittney M. J.; Zhang, Jing; Zhang, Ping; Duan, Dehui; Nolan, Christina K.; Sciotti, Richard J.; Zottig, Victor E.; Nanayakkara, N. P. Dhammika; Tekwani, Babu L.; Walker, Larry A.; Smith, Philip L.; Paris, Robert M.; Read, Lisa T.; Li, Qigui; Pybus, Brandon S.; Sousa, Jason C.; Reichard, Gregory A.; Smith, Bryan

2015-01-01

Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial efficacy of the 8-aminoquinoline molecule tafenoquine in mice. This could be problematic for Plasmodium vivax radical cure, as the human CYP 2D ortholog (2D6) is highly polymorphic. Diminished CYP 2D6 enzyme activity, as in the poor-metabolizer phenotype, could compromise radical curative efficacy in humans. Despite the importance of CYP 2D metabolism for tafenoquine liver-stage efficacy, the exact role that CYP 2D metabolism plays in the metabolism and pharmacokinetics of tafenoquine and other 8-aminoquinoline molecules has not been extensively studied. In this study, a series of tafenoquine pharmacokinetic experiments were conducted in mice with different CYP 2D metabolism statuses, including wild-type (WT) (reflecting extensive metabolizers for CYP 2D6 substrates) and CYPmouse 2D knockout (KO) (reflecting poor metabolizers for CYP 2D6 substrates) mice. Plasma and liver pharmacokinetic profiles from a single 20-mg/kg of body weight dose of tafenoquine differed between the strains; however, the differences were less striking than previous results obtained for primaquine in the same model. Additionally, the presence of a 5,6-ortho-quinone tafenoquine metabolite was examined in both mouse strains. The 5,6-ortho-quinone species of tafenoquine was observed, and concentrations of the metabolite were highest in the WT extensive-metabolizer phenotype. Altogether, this study indicates that CYP 2D metabolism in mice affects tafenoquine pharmacokinetics and could have implications for human tafenoquine pharmacokinetics in polymorphic CYP 2D6 human populations. PMID:25870069

Pyrroloquinoline quinone (PQQ) is reduced to pyrroloquinoline quinol (PQQH2) by vitamin C, and PQQH2 produced is recycled to PQQ by air oxidation in buffer solution at pH 7.4.

PubMed

Mukai, Kazuo; Ouchi, Aya; Nagaoka, Shin-ichi; Nakano, Masahiko; Ikemoto, Kazuto

2016-01-01

Measurements of the reaction of sodium salt of pyrroloquinoline quinone (PQQNa2) with vitamin C (Vit C) were performed in phosphate-buffered solution (pH 7.4) at 25 °C under nitrogen atmosphere, using UV-vis spectrophotometry. The absorption spectrum of PQQNa2 decreased in intensity due to the reaction with Vit C and was changed to that of pyrroloquinoline quinol (PQQH2, a reduced form of PQQ). One molecule of PQQ was reduced by two molecules of Vit C producing a molecule of PQQH2 in the buffer solution. PQQH2, thus produced, was recycled to PQQ due to air oxidation. PQQ and Vit C coexist in many biological systems, such as vegetables, fruits, as well as in human tissues. The results obtained suggest that PQQ is reduced by Vit C and functions as an antioxidant in biological systems, because it has been reported that PQQH2 shows very high free-radical scavenging and singlet-oxygen quenching activities in buffer solutions.

Molecular complexes of l-phenylalanine with substituted 1,4-benzoquinones in aqueous medium: spectral and theoretical investigations.

PubMed

Ganesh, K; El-Mossalamy, E H; Satheshkumar, A; Balraj, C; Elango, K P

2013-12-01

Various spectral techniques such as UV-Vis, FT-IR, and fluorescence have been employed to investigate the charge transfer interaction of L-phenylalanine (LPA) with substituted 1,4-benzoquinones (MQ(1-4)). Kinetic and thermodynamic properties of the complexes were determined in aqueous medium at physiological condition (pH=7). The interaction of MQ(1-4) with L-phenylalanine (LPA) was found to proceed through the formation of donor-acceptor complex, yielding a radical anion. The stoichiometry of the complexes was determined by Jobs continuous variation method and was found to be 1:1 in all the cases. Fluorescence quenching studies showed that the interaction between the donor and the acceptors is spontaneous. The results indicated that the progressive replacement of chlorine atom (-I effect) by methoxy group (+M effect) in the quinone decreased the electron acceptor property of the quinone. The order of the experimentally measured association constant of these complexes was well supported by DFT/B3LYP calculations. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydroxynaphthoquinone ultrathin films obtained by diazonium electroreduction: toward design of biosensitive electroactive interfaces.

PubMed

March, Gregory; Reisberg, Steeve; Piro, Benoit; Pham, Minh-Chau; Fave, Claire; Noel, Vincent

2010-05-01

Electroactive 2-(phenylsulfanyl)-8-hydroxy-1,4-naphthoquinone has been electrodeposited via the reduction of the corresponding diazonium salt on Au electrodes. Surface characterizations by X-ray photoelectron spectroscopy (XPS) and infrared reflection-absorption spectroscopy (IRRAS) reveal that the mechanism of film deposition follows an aryl radical formation and its immobilization on the electrode surface. Electrochemical study shows that the surface coverage can be finely tuned (thickness between one and four layers) by adjusting the potential and the deposition time. By managing the potential applied when reducing diazonium in potentiostatic mode, the formed layer could mediate or not charge transfer. This is the first time that the films obtained by diazonium process are demonstrated to act as mediators in the growth process. Hence, with potentials higher than the formal potential of quinone group, very thin and homogeneous layers are obtained, whereas thicker films are formed when more cathodic potentials than that of quinone are applied. The possibility to manage the charge-transfer kinetics, the thickness, and the homogeneity of electroactive deposits is interesting in the scope of designing electrochemical transducers.

Nature of electrogenerated intermediates in nitro-substituted nor-β-lapachones: the structure of radical species during successive electron transfer in multiredox centers.

PubMed

Armendáriz-Vidales, Georgina; Hernández-Muñoz, Lindsay S; González, Felipe J; de Souza, Antonio A; de Abreu, Fabiane C; Jardim, Guilherme A M; da Silva, Eufrânio N; Goulart, Marilia O F; Frontana, Carlos

2014-06-06

Electrochemical, spectroelectrochemical, and theoretical studies of the reduction reactions in nor-β-lapachone derivatives including a nitro redox center showed that reduction of the compounds involves the formation of several radical intermediates, including a biradical dianion resultant from the separate reduction of the quinone and nitro groups in the molecules. Theoretical descriptions of the corresponding Fukui functions f(αα)⁺ and f(ββ)⁺(r) and LUMO densities considering finite differences and frozen core approximations for describing the changes in electron and spin densities of the system allowed us to confirm these results. A description of the potential relationship with the obtained results and biological activity selectivity indexes suggests that both the formation of stable biradical dianion species and the stability of the semiquinone intermediates during further reduction are determining factors in the description of their biological activity.

A New Look on Protein-Polyphenol Complexation during Honey Storage: Is This a Random or Organized Event with the Help of Dirigent-Like Proteins?

PubMed Central

Brudzynski, Katrina; Sjaarda, Calvin; Maldonado-Alvarez, Liset

2013-01-01

Honey storage initiates melanoidin formation that involves a cascade of seemingly unguided redox reactions between amino acids/proteins, reducing sugars and polyphenols. In the process, high molecular weight protein-polyphenol complexes are formed, but the mechanism involved remains unknown. The objective of this study was twofold: to determine quantitative and qualitative changes in proteins in honeys stored for prolonged times and in different temperatures and to relate these changes to the formation of protein-polyphenol complexes. Six -month storage decreased the protein content by 46.7% in all tested honeys (t-test, p<0.002) with the rapid reduction occurring during the first three month. The changes in protein levels coincided with alterations in molecular size and net charge of proteins on SDS –PAGE. Electro-blotted proteins reacted with a quinone-specific nitro blue tetrazolium (NBT) on nitrocellulose membranes indicating that quinones derived from oxidized polyphenols formed covalent bonds with proteins. Protein-polyphenol complexes isolated by size-exclusion chromatography differed in size and stoichiometry and fall into two categories: (a) high molecular weight complexes (230–180 kDa) enriched in proteins but possessing a limited reducing activity toward the NBT and (b) lower molecular size complexes (110–85 kDa) enriched in polyphenols but strongly reducing the dye. The variable stoichiometry suggest that the large, “protein-type” complexes were formed by protein cross-linking, while in the smaller, “polyphenol-type” complexes polyphenols were first polymerized prior to protein binding. Quinones preferentially bound a 31 kDa protein which, by the electrospray quadrupole time of flight mass spectrometry (ESI-Qtof-MS) analysis, showed homology to dirigent-like proteins known for assisting in radical coupling and polymerization of phenolic compounds. These findings provide a new look on protein-polyphenol interaction in honey where the reaction of quinones with proteins and polyphenols could possibly be under assumed guidance of dirigent proteins. PMID:24023654

A new look on protein-polyphenol complexation during honey storage: is this a random or organized event with the help of dirigent-like proteins?

PubMed

Brudzynski, Katrina; Sjaarda, Calvin; Maldonado-Alvarez, Liset

2013-01-01

Honey storage initiates melanoidin formation that involves a cascade of seemingly unguided redox reactions between amino acids/proteins, reducing sugars and polyphenols. In the process, high molecular weight protein-polyphenol complexes are formed, but the mechanism involved remains unknown. The objective of this study was twofold: to determine quantitative and qualitative changes in proteins in honeys stored for prolonged times and in different temperatures and to relate these changes to the formation of protein-polyphenol complexes. Six -month storage decreased the protein content by 46.7% in all tested honeys (t-test, p<0.002) with the rapid reduction occurring during the first three month. The changes in protein levels coincided with alterations in molecular size and net charge of proteins on SDS -PAGE. Electro-blotted proteins reacted with a quinone-specific nitro blue tetrazolium (NBT) on nitrocellulose membranes indicating that quinones derived from oxidized polyphenols formed covalent bonds with proteins. Protein-polyphenol complexes isolated by size-exclusion chromatography differed in size and stoichiometry and fall into two categories: (a) high molecular weight complexes (230-180 kDa) enriched in proteins but possessing a limited reducing activity toward the NBT and (b) lower molecular size complexes (110-85 kDa) enriched in polyphenols but strongly reducing the dye. The variable stoichiometry suggest that the large, "protein-type" complexes were formed by protein cross-linking, while in the smaller, "polyphenol-type" complexes polyphenols were first polymerized prior to protein binding. Quinones preferentially bound a 31 kDa protein which, by the electrospray quadrupole time of flight mass spectrometry (ESI-Qtof-MS) analysis, showed homology to dirigent-like proteins known for assisting in radical coupling and polymerization of phenolic compounds. These findings provide a new look on protein-polyphenol interaction in honey where the reaction of quinones with proteins and polyphenols could possibly be under assumed guidance of dirigent proteins.

Kinetic modeling of electron transfer reactions in photosystem I complexes of various structures with substituted quinone acceptors.

PubMed

Milanovsky, Georgy E; Petrova, Anastasia A; Cherepanov, Dmitry A; Semenov, Alexey Yu

2017-09-01

The reduction kinetics of the photo-oxidized primary electron donor P 700 in photosystem I (PS I) complexes from cyanobacteria Synechocystis sp. PCC 6803 were analyzed within the kinetic model, which considers electron transfer (ET) reactions between P 700 , secondary quinone acceptor A 1 , iron-sulfur clusters and external electron donor and acceptors - methylviologen (MV), 2,3-dichloro-naphthoquinone (Cl 2 NQ) and oxygen. PS I complexes containing various quinones in the A 1 -binding site (phylloquinone PhQ, plastoquinone-9 PQ and Cl 2 NQ) as well as F X -core complexes, depleted of terminal iron-sulfur F A /F B clusters, were studied. The acceleration of charge recombination in F X -core complexes by PhQ/PQ substitution indicates that backward ET from the iron-sulfur clusters involves quinone in the A 1 -binding site. The kinetic parameters of ET reactions were obtained by global fitting of the P 700 + reduction with the kinetic model. The free energy gap ΔG 0 between F X and F A /F B clusters was estimated as -130 meV. The driving force of ET from A 1 to F X was determined as -50 and -220 meV for PhQ in the A and B cofactor branches, respectively. For PQ in A 1A -site, this reaction was found to be endergonic (ΔG 0  = +75 meV). The interaction of PS I with external acceptors was quantitatively described in terms of Michaelis-Menten kinetics. The second-order rate constants of ET from F A /F B , F X and Cl 2 NQ in the A 1 -site of PS I to external acceptors were estimated. The side production of superoxide radical in the A 1 -site by oxygen reduction via the Mehler reaction might comprise ≥0.3% of the total electron flow in PS I.

Identification of the residues involved in stabilization of the semiquinone radical in the high-affinity ubiquinone binding site in cytochrome bo(3) from Escherichia coli by site-directed mutagenesis and EPR spectroscopy.

PubMed

Hellwig, Petra; Yano, Takahiro; Ohnishi, Tomoko; Gennis, Robert B

2002-08-27

During turnover of cytochrome bo(3) from Escherichia coli, a semiquinone radical is stabilized in a high-affinity binding site. To identify binding partners of this radical, site-directed mutants have been designed on the basis of a recently modeled quinone binding site (Abramson et al., 2000). The R71H, H98F, D75H, and I102W mutant enzymes were found to show very little or no quinol oxidase activity. The thermodynamic and EPR spectroscopic properties of semiquinone radicals in these mutants were characterized. For the H98F and the R71H mutants, no EPR signal of the semiquinone radical was observed in the redox potential range from -100 to 250 mV. During potentiometric titration of the D75H mutant enzyme, a semiquinone signal was detected in the same potential range as that of the wild-type enzyme. However, the EPR spectrum of the D75H mutant lacks the characteristic hyperfine structure of the semiquinone radical signal observed in the wild-type oxidase, indicating that D75 or the introduced His, interacts with the semiquinone radical. For the I102W mutant, a free radical signal was observed with a redox midpoint potential downshifted by about 200 mV. On the basis of these observations, it is suggested that R71, D75, and H98 residues are involved in the stabilization of the semiquinone state in the high-affinity binding site. Details of the possible binding motif and mechanistic implications are discussed.

Dynamic nuclear polarization-magnetic resonance imaging at low ESR irradiation frequency for ascorbyl free radicals.

PubMed

Ito, Shinji; Hyodo, Fuminori

2016-02-19

Highly water-soluble ubiquinone-0 (CoQ0) reacts with ascorbate monoanion (Asc) to mediate the production of ascorbyl free radicals (AFR). Using aqueous reaction mixture of CoQ0 and Asc, we obtained positively enhanced dynamic nuclear polarization (DNP)-magnetic resonance (MR) images of the AFR at low frequency (ranging from 515 to 530 MHz) of electron spin resonance (ESR) irradiation. The shape of the determined DNP spectrum was similar to ESR absorption spectra with doublet spectral peaks. The relative locational relationship of spectral peaks in the DNP spectra between the AFR (520 and 525 MHz), (14)N-labeled carbamoyl-PROXYL ((14)N-CmP) (526.5 MHz), and Oxo63 (522 MHz) was different from that in the X-band ESR spectra, but were similar to that in the 300-MHz ESR spectra. The ratio of DNP enhancement to radical concentration for the AFR was higher than those for (14)N-CmP, Oxo63, and flavin semiquinone radicals. The spectroscopic DNP properties observed for the AFR were essentially the same as those for AFR mediated by pyrroloquinoline quinone. Moreover, we made a success of in vivo DNP-MR imaging of the CoQ0-mediated AFR which was administered by the subcutaneous and oral injections as an imaging probe.

Quinone Reductase 2 Is a Catechol Quinone Reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 betweenmore » 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.« less

pH-Dependent Regulation of the Relaxation Rate of the Radical Anion of the Secondary Quinone Electron Acceptor QB in Photosystem II As Revealed by Fourier Transform Infrared Spectroscopy.

PubMed

Nozawa, Yosuke; Noguchi, Takumi

2018-05-15

Photosystem II (PSII) is a protein complex that performs water oxidation using light energy during photosynthesis. In PSII, electrons abstracted from water are eventually transferred to the secondary quinone electron acceptor, Q B , and upon double reduction, Q B is converted to quinol by binding two protons. Thus, excess electron transfer in PSII increases the pH of the stroma. In this study, to investigate the pH-dependent regulation of the electron flow in PSII, we have estimated the relaxation rate of the Q B - radical anion in the pH region between 5 and 8 by direct monitoring of its population using light-induced Fourier transform infrared difference spectroscopy. The decay of Q B - by charge recombination with the S 2 state of the water oxidation center in PSII membranes was shown to be accelerated at higher pH, whereas that of Q A - examined in the presence of a herbicide was virtually unaffected at pH ≤7.5 and slightly slowed at pH 8. These observations were consistent with the previous studies that included rather indirect monitoring of the Q B - and Q A - decays using fluorescence detection. The accelerated relaxation of Q B - was explained by the shift of a redox equilibrium between Q A - and Q B - to the Q A - side due to the decrease in the redox potential of Q B at higher pH, which is induced by deprotonation of a single amino acid residue near Q B . It is proposed that this pH-dependent Q B - relaxation is one of the mechanisms of electron flow regulation in PSII for its photoprotection.

Differential cytochrome P450 2D metabolism alters tafenoquine pharmacokinetics.

PubMed

Vuong, Chau; Xie, Lisa H; Potter, Brittney M J; Zhang, Jing; Zhang, Ping; Duan, Dehui; Nolan, Christina K; Sciotti, Richard J; Zottig, Victor E; Nanayakkara, N P Dhammika; Tekwani, Babu L; Walker, Larry A; Smith, Philip L; Paris, Robert M; Read, Lisa T; Li, Qigui; Pybus, Brandon S; Sousa, Jason C; Reichard, Gregory A; Smith, Bryan; Marcsisin, Sean R

2015-07-01

Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial efficacy of the 8-aminoquinoline molecule tafenoquine in mice. This could be problematic for Plasmodium vivax radical cure, as the human CYP 2D ortholog (2D6) is highly polymorphic. Diminished CYP 2D6 enzyme activity, as in the poor-metabolizer phenotype, could compromise radical curative efficacy in humans. Despite the importance of CYP 2D metabolism for tafenoquine liver-stage efficacy, the exact role that CYP 2D metabolism plays in the metabolism and pharmacokinetics of tafenoquine and other 8-aminoquinoline molecules has not been extensively studied. In this study, a series of tafenoquine pharmacokinetic experiments were conducted in mice with different CYP 2D metabolism statuses, including wild-type (WT) (reflecting extensive metabolizers for CYP 2D6 substrates) and CYPmouse 2D knockout (KO) (reflecting poor metabolizers for CYP 2D6 substrates) mice. Plasma and liver pharmacokinetic profiles from a single 20-mg/kg of body weight dose of tafenoquine differed between the strains; however, the differences were less striking than previous results obtained for primaquine in the same model. Additionally, the presence of a 5,6-ortho-quinone tafenoquine metabolite was examined in both mouse strains. The 5,6-ortho-quinone species of tafenoquine was observed, and concentrations of the metabolite were highest in the WT extensive-metabolizer phenotype. Altogether, this study indicates that CYP 2D metabolism in mice affects tafenoquine pharmacokinetics and could have implications for human tafenoquine pharmacokinetics in polymorphic CYP 2D6 human populations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Low-energy electron interaction with retusin extracted from Maackia amurensis: towards a molecular mechanism of the biological activity of flavonoids.

PubMed

Pshenichnyuk, Stanislav A; Elkin, Yury N; Kulesh, Nadezda I; Lazneva, Eleonora F; Komolov, Alexei S

2015-07-14

The antioxidant isoflavone retusin efficiently attaches low-energy electrons in vacuo, generating fragment species via dissociative electron attachment (DEA), as has been shown by DEA spectroscopy. According to in silico results obtained by means of density functional theory, retusin is able to attach solvated electrons and could be decomposed under reductive conditions in vivo, for instance, near the mitochondrial electron transport chain, analogous to gas-phase DEA. The most intense decay channels of retusin temporary negative ions were found to be associated with the elimination of H atoms and H2 molecules. Doubly dehydrogenated fragment anions were predicted to possess a quinone structure. It is thought that molecular hydrogen, known for its selective antioxidant properties, can be efficiently generated via electron attachment to retusin in mitochondria and may be responsible for its antioxidant activity. The second abundant species, i.e., quinone bearing an excess negative charge, can serve as an electron carrier and can return the captured electron back to the respiration cycle. The number of OH substituents and their relative positions are crucial for the present molecular mechanism, which can explain the radical scavenging activity of polyphenolic compounds.

Homolytic Cleavage of a B-B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification.

PubMed

Wang, Guoqiang; Zhang, Honglin; Zhao, Jiyang; Li, Wei; Cao, Jia; Zhu, Chengjian; Li, Shuhua

2016-05-10

Density functional theory (DFT) investigations revealed that 4-cyanopyridine was capable of homolytically cleaving the B-B σ bond of diborane via the cooperative coordination to the two boron atoms of the diborane to generate pyridine boryl radicals. Our experimental verification provides supportive evidence for this new B-B activation mode. With this novel activation strategy, we have experimentally realized the catalytic reduction of azo-compounds to hydrazine derivatives, deoxygenation of sulfoxides to sulfides, and reduction of quinones with B2 (pin)2 at mild conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Phytochemical screening and analysis of antioxidant properties of aqueous extract of wheatgrass.

PubMed

Durairaj, Varalakshmi; Hoda, Muddasarul; Shakya, Garima; Babu, Sankar Pajaniradje Preedia; Rajagopalan, Rukkumani

2014-09-01

To screen the phytochemical constituents and study antioxidant properties of the aqueous extract of the wheatgrass. The current study was focused on broad parameters namely, phytochemical analysis, gas chromatography-mass spectrometry analysis and antioxidant properties in order to characterize the aqueous extract of wheatgrass as a potential free radical quencher. The phytochemical screening of the aqueous extract of wheatgrass showed the presence of various secondary metabolites but the absence of sterols and quinone in general. Wheatgrass was proved to be an effective radical scavenger in all antioxidant assays. The gas chromatography-mass spectrometry analysis confirmed the presence of diverse category of bioactive compounds such as squalene, caryophyllene and amyrins in varying percentage. From the results obtained, we conclude that wheatgrass aqueous extract contains various effective compounds. It is a potential source of natural antioxidants. Further analysis of this herb will help in finding new effective compounds which can be of potent use in pharmacological field. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites

PubMed Central

Hoshino, Juma; Park, Eun-Jung; Kondratyuk, Tamara P.; Marler, Laura; Pezzuto, John M.; van Breemen, Richard B.; Mo, Shunyan; Li, Yongchao; Cushman, Mark

2010-01-01

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)-α-induced NFκB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, and proliferation of KB or MCF7 cells, induction of quinone reductase 1 (QR1), accumulation in the sub-G1 phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QR1 induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities, and the 4′-sulfate inhibited NFκB induction, as well as COX-1 and COX-2 activities. Resveratrol, as well as its 3′-sulfate and 4-sulfate, inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells. PMID:20527891

Autoxidative and Cyclooxygenase-2 Catalyzed Transformation of the Dietary Chemopreventive Agent Curcumin*

PubMed Central

Griesser, Markus; Pistis, Valentina; Suzuki, Takashi; Tejera, Noemi; Pratt, Derek A.; Schneider, Claus

2011-01-01

The efficacy of the diphenol curcumin as a cancer chemopreventive agent is limited by its chemical and metabolic instability. Non-enzymatic degradation has been described to yield vanillin, ferulic acid, and feruloylmethane through cleavage of the heptadienone chain connecting the phenolic rings. Here we provide evidence for an alternative mechanism, resulting in autoxidative cyclization of the heptadienone moiety as a major pathway of degradation. Autoxidative transformation of curcumin was pH-dependent with the highest rate at pH 8 (2.2 μm/min) and associated with stoichiometric uptake of O2. Oxidation was also catalyzed by recombinant cyclooxygenase-2 (COX-2) (50 nm; 7.5 μm/min), and the rate was increased ≈10-fold by the addition of 300 μm H2O2. The COX-2 catalyzed transformation was inhibited by acetaminophen but not indomethacin, suggesting catalysis occurred by the peroxidase activity. We propose a mechanism of enzymatic or autoxidative hydrogen abstraction from a phenolic hydroxyl to give a quinone methide and a delocalized radical in the heptadienone chain that undergoes 5-exo cyclization and oxygenation. Hydration of the quinone methide (measured by the incorporation of O-18 from H218O) and rearrangement under loss of water gives the final dioxygenated bicyclopentadione product. When curcumin was added to RAW264.7 cells, the bicyclopentadione was increased 1.8-fold in cells activated by LPS; vanillin and other putative cleavage products were negligible. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. It is possible, therefore, that oxidative transformation of curcumin, a prominent but previously unrecognized reaction, contributes to its cancer chemopreventive activity. PMID:21071447

Bioinspired organocatalytic aerobic C-H oxidation of amines with an ortho-quinone catalyst.

PubMed

Qin, Yan; Zhang, Long; Lv, Jian; Luo, Sanzhong; Cheng, Jin-Pei

2015-03-20

A simple bioinspired ortho-quinone catalyst for the aerobic oxidative dehydrogenation of amines to imines is reported. Without any metal cocatalysts, the identified optimal ortho-quinone catalyst enables the oxidations of α-branched primary amines and cyclic secondary amines. Mechanistic studies have disclosed the origins of different performances of ortho-quinone vs para-quinone in biomimetic amine oxidations.

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 13C abundance in the quinone. In this study, we verified carbon stable isotope of quinone compared with bulk carbon stable isotope of bacterial culture. Results indicated a good correlation between carbon stable isotope of quinone compared with bulk carbon stable isotope. However, our measurement conditions for detection of quinone isotope-ions incurred underestimation of 13C abundance in the quinone. The quinone-SIP technique needs further optimization for measurement conditions of LC-MS/MS.

Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.

PubMed

Kogan, Natalya M; Rabinowitz, Ruth; Levi, Paloma; Gibson, Dan; Sandor, Peter; Schlesinger, Michael; Mechoulam, Raphael

2004-07-15

Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.

Evaluation of hydrological processes in a mountainous small basin using a quinone biomarker.

PubMed

Fujita, M; Haga, H; Nishida, K; Sakamoto, Y

2006-01-01

An applicability of quinone biomarker to the analysis of hillslope runoff was investigated. At first, quinone profiles of three streams as well as a hillslope runoff in a forested headwater catchment were compared. The quinone composition of hillslope runoff differed from others. Moreover, there were remarkable differences in quinone profile of hillslope runoff under different rainfall conditions. Then, the behavior of quinone biomarker during the increase and decrease of hillslope runoff after a rainfall event was examined. The fractional changes in Q-9 (H2), Q-10 (H2), Q-11, MK-6 and MK-10 suggested the effect of interflow.

[Development of selective determination methods for quinones with fluorescence and chemiluminescence detection and their application to environmental and biological samples].

PubMed

Kishikawa, Naoya

2010-10-01

Quinones are compounds that have various characteristics such as a biological electron transporter, an industrial product and a harmful environmental pollutant. Therefore, an effective determination method for quinones is required in many fields. This review describes the development of sensitive and selective determination methods for quinones based on some detection principles and their application to analyses in environmental, pharmaceutical and biological samples. Firstly, a fluorescence method was developed based on fluorogenic derivatization of quinones and applied to environmental analysis. Secondly, a luminol chemiluminescence method was developed based on generation of reactive oxygen species through the redox cycle of quinone and applied to pharmaceutical analysis. Thirdly, a photo-induced chemiluminescence method was developed based on formation of reactive oxygen species and fluorophore or chemiluminescence enhancer by the photoreaction of quinones and applied to biological and environmental analyses.

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

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. © 2014 John Wiley & Sons Ltd.

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

PubMed

Wnorowski, Andrzej; Charland, Jean-Pierre

2017-12-01

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 NO x 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.

Synthesis of a water-soluble analog of 6-methyl-3-N-alkyl catechol labeled with carbon 13: NMR approach to the reactivity of poison ivy/oak sensitizers toward proteins.

PubMed

Goetz, G; Meschkat, E; Lepoittevin, J P

1999-04-19

A 13-C labeled water soluble derivative of alkylcatechol was synthesized and reacted with human serum albumin in phosphate buffer at pH 7.4 in air to allow a slow oxidation of the catechol into orthoquinone. The formation of several adducts was evidenced by a combination of 13C and 1H-13C correlation NMR. Although some adducts could result from a classical o-quinone formation - Michael type addition, our results suggest that a second pathway, involving a direct reaction of a carbon centered radical with proteins could be an important mechanism in the formation of modified proteins.

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

On-column reduction of catecholamine quinones in stainless steel columns during liquid chromatography.

PubMed

Xu, R; Huang, X; Kramer, K J; Hawley, M D

1995-10-10

The chromatographic behavior of quinones derived from the oxidation of dopamine and N-acetyldopamine has been studied using liquid chromatography (LC) with both a diode array detector and an electrochemical detector that has parallel dual working electrodes. When stainless steel columns are used, an anodic peak for the oxidation of the catecholamine is observed at the same retention time as a cathodic peak for the reduction of the catecholamine quinone. In addition, the anodic peak exhibits a tail that extends to a second anodic peak for the catecholamine. The latter peak occurs at the normal retention time of the catecholamine. The origin of this phenomenon has been studied and metallic iron in the stainless steel components of the LC system has been found to reduce the quinones to their corresponding catecholamines. The simultaneous appearance of a cathodic peak for the reduction of catecholamine quinone and an anodic peak for the oxidation of the corresponding catecholamine occurs when metallic iron in the exit frit reduces some of the quinones as the latter exits the column. This phenomenon is designated as the "concurrent anodic-cathodic response." It is also observed for quinones of of 3,4-dihydroxybenzoic acid and probably occurs with o- or p-quinones of other dihydroxyphenyl compounds. The use of nonferrous components in LC systems is recommended to eliminate possible on-column reduction of quinones.

A Key Role for Old Yellow Enzyme in the Metabolism of Drugs by Trypanosoma cruzi

PubMed Central

Kubata, Bruno Kilunga; Kabututu, Zakayi; Nozaki, Tomoyoshi; Munday, Craig J.; Fukuzumi, Shunichi; Ohkubo, Kei; Lazarus, Michael; Maruyama, Toshihiko; Martin, Samuel K.; Duszenko, Michael; Urade, Yoshihiro

2002-01-01

Trypanosoma cruzi is the etiological agent of Chagas' disease. So far, first choice anti-chagasic drugs in use have been shown to have undesirable side effects in addition to the emergence of parasite resistance and the lack of prospect for vaccine against T. cruzi infection. Thus, the isolation and characterization of molecules essential in parasite metabolism of the anti-chagasic drugs are fundamental for the development of new strategies for rational drug design and/or the improvement of the current chemotherapy. While searching for a prostaglandin (PG) F2α synthase homologue, we have identified a novel “old yellow enzyme” from T. cruzi (TcOYE), cloned its cDNA, and overexpressed the recombinant enzyme. Here, we show that TcOYE reduced 9,11-endoperoxide PGH2 to PGF2α as well as a variety of trypanocidal drugs. By electron spin resonance experiments, we found that TcOYE specifically catalyzed one-electron reduction of menadione and β-lapachone to semiquinone-free radicals with concomitant generation of superoxide radical anions, while catalyzing solely the two-electron reduction of nifurtimox and 4-nitroquinoline-N-oxide drugs without free radical production. Interestingly, immunoprecipitation experiments revealed that anti-TcOYE polyclonal antibody abolished major reductase activities of the lysates toward these drugs, identifying TcOYE as a key drug-metabolizing enzyme by which quinone drugs have their mechanism of action. PMID:12417633

Antioxidant and drug detoxification potentials of Hibiscus sabdariffa anthocyanin extract.

PubMed

Ajiboye, Taofeek O; Salawu, Nasir A; Yakubu, Musa T; Oladiji, Adenike T; Akanji, Musbau A; Okogun, Joseph I

2011-04-01

The antioxidant and drug metabolizing potentials of Hibiscus anthocyanin extract in CCl(4)- induced oxidative damage of rat liver was investigated. Hibiscus anthocyanin extract effectively scavenge α-diphenyl-β-picrylhydrazyl (DPPH) radical, superoxide ion, and hydrogen peroxide. It produced a 92% scavenging effect of DPPH radical at a concentration of 2.0 mg/mL. Hibiscus anthocyanin extract produced a 69 and 90% scavenging effect on superoxide ion and hydrogen peroxide, respectively, at 1.0 mg/mL, which compared favorably with the synthetic antioxidant (butylated hydroanisole and α-tocopherol). A reducing power of this anthocyanin was examined using K(3)Fe(CN)(6). Hibiscus anthocyanin extract has reducing power that is approximately 2-fold that of the synthetic antioxidant, butylated hydroanisole. Hibiscus anthocyanin extract produced a significantly increase and completely attenuated the CCl(4)-mediated decrease in antioxidant enzymes (e.g., catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). However, the level of nonenzymic antioxidant molecules (i.e., vitamins C and E) were significant preserved by Hibiscus anthocyanin extract. There was an induction of phase II drug-detoxifying enzymes: glutathione S-transferase, NAD(H):quinone oxidoreductase, and uridyl diphosphoglucuronosyl transferase by 65, 45, and 57%, respectively. In view of these properties, Hibiscus sabdariffa anthocyanin extract can act as a prophylactic by intervening as a free radical scavenger both in vitro and in vivo as well as inducing the phase II drug detoxification enzymes.

Quinone 1 e – and 2 e – /2 H + Reduction Potentials: Identification and Analysis of Deviations from Systematic Scaling Relationships

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huynh, Mioy T.; Anson, Colin W.; Cavell, Andrew C.

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 formore » 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.« less

Computational design of molecules for an all-quinone redox flow battery† †Electronic supplementary information (ESI) available: The list of computationally predicted candidate quinone molecules with interesting redox properties. See DOI: 10.1039/c4sc03030c Click here for additional data file.

PubMed Central

Er, Süleyman; Suh, Changwon; Marshak, Michael P.

2015-01-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH2) (i.e., two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships. PMID:29560173

Role of chlorogenic acid quinone and interaction of chlorogenic acid quinone and catechins in the enzymatic browning of apple.

PubMed

Amaki, Kanako; Saito, Eri; Taniguchi, Kumiko; Joshita, Keiko; Murata, Masatsune

2011-01-01

Chlorogenic acid (CQA) is one of the major polyphenols in apple and a good substrate for the polyphenol oxidase (PPO) in apple. Apple contains catechins as well as CQA, and the role of CQA quinone and its interaction with catechins in the enzymatic browning of apple were examined. Browning was repressed and 2-cysteinyl-CQA was formed when cysteine was added to apple juice. CQA quinone was essential for browning to occur. Although catechins and CQA were oxidized by PPO, some catechins seemed to be non-enzymatically oxidized by CQA quinone.

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.

Reduction of Clofazimine by Mycobacterial Type 2 NADH:Quinone Oxidoreductase

PubMed Central

Yano, Takahiro; Kassovska-Bratinova, Sacha; Teh, J. Shin; Winkler, Jeffrey; Sullivan, Kevin; Isaacs, Andre; Schechter, Norman M.; Rubin, Harvey

2011-01-01

The mechanism of action of clofazimine (CFZ), an antimycobacterial drug with a long history, is not well understood. The present study describes a redox cycling pathway that involves the enzymatic reduction of CFZ by NDH-2, the primary respiratory chain NADH:quinone oxidoreductase of mycobacteria and nonenzymatic oxidation of reduced CFZ by O2 yielding CFZ and reactive oxygen species (ROS). This pathway was demonstrated using isolated membranes and purified recombinant NDH-2. The reduction and oxidation of CFZ was measured spectrally, and the production of ROS was measured using a coupled assay system with Amplex Red. Supporting the ROS-based killing mechanism, bacteria grown in the presence of antioxidants are more resistant to CFZ. CFZ-mediated increase in NADH oxidation and ROS production were not observed in membranes from three different Gram-negative bacteria but was observed in Staphylococcus aureus and Saccharomyces cerevisiae, which is consistent with the known antimicrobial specificity of CFZ. A more soluble analog of CFZ, KS6, was synthesized and was shown to have the same activities as CFZ. These studies describe a pathway for a continuous and high rate of reactive oxygen species production in Mycobacterium smegmatis treated with CFZ and a CFZ analog as well as evidence that cell death produced by these agents are related to the production of these radical species. PMID:21193400

Humic acids: Structural properties and multiple functionalities for novel technological developments.

PubMed

de Melo, Bruna Alice Gomes; Motta, Fernanda Lopes; Santana, Maria Helena Andrade

2016-05-01

Humic acids (HAs) are macromolecules that comprise humic substances (HS), which are organic matter distributed in terrestrial soil, natural water, and sediment. HAs differ from the other HS fractions (fulvic acid and humins) in that they are soluble in alkaline media, partially soluble in water, and insoluble in acidic media. Due to their amphiphilic character, HAs form micelle-like structures in neutral to acidic conditions, which are useful in agriculture, pollution remediation, medicine and pharmaceuticals. HAs have undefined compositions that vary according to the origin, process of obtainment, and functional groups present in their structures, such as quinones, phenols, and carboxylic acids. Quinones are responsible for the formation of reactive oxygen species (ROS) in HAs, which are useful for wound healing and have fungicidal/bactericidal properties. Phenols and carboxylic acids deprotonate in neutral and alkaline media and are responsible for various other functions, such as the antioxidant and anti-inflammatory properties of HAs. In particular, the presence of phenolic groups in HAs provides antioxidant properties due to their free radical scavenging capacity. This paper describes the main multifunctionalities of HAs associated with their structures and properties, focusing on human health applications, and we note perspectives that may lead to novel technological developments. To the best of our knowledge, this is the first review to address this topic from this approach. Copyright © 2015 Elsevier B.V. All rights reserved.

4-Hydroxylated metabolites of the antiestrogens tamoxifen and toremifene are metabolized to unusually stable quinone methides.

PubMed

Fan, P W; Zhang, F; Bolton, J L

2000-01-01

Tamoxifen is widely prescribed for the treatment of hormone-dependent breast cancer, and it has recently been approved by the Food and Drug Administration for the chemoprevention of this disease. However, long-term usage of tamoxifen has been linked to increased risk of developing endometrial cancer in women. One of the suggested pathways leading to the potential toxicity of tamoxifen involves its oxidative metabolism to 4-hydroxytamoxifen, which may be further oxidized to an electrophilic quinone methide. The resulting quinone methide has the potential to alkylate DNA and may initiate the carcinogenic process. To further probe the chemical reactivity and toxicity of such an electrophilic species, we have prepared the 4-hydroxytamoxifen quinone methide chemically and enzymatically, examined its reactivity under physiological conditions, and quantified its reactivity with GSH. Interestingly, this quinone methide is unusually stable; its half-life under physiological conditions is approximately 3 h, and its half-life in the presence of GSH is approximately 4 min. The reaction between 4-hydroxytamoxifen quinone methide and GSH appears to be a reversible process because the quinone methide GSH conjugates slowly decompose over time, regenerating the quinone methide as indicated by LC/MS/MS data. The tamoxifen GSH conjugates were detected in microsomal incubations with 4-hydroxytamoxifen; however, none were observed in breast cancer cell lines (MCF-7) perhaps because very little quinone methides is formed. Toremifene, which is a chlorinated analogue of tamoxifen, undergoes similar oxidative metabolism to give 4-hydroxytoremifene, which is further oxidized to the corresponding quinone methide. The toremifene quinone methide has a half-life of approximately 1 h under physiological conditions, and its rate of reaction in the presence of excess GSH is approximately 6 min. More detailed analyses have indicated that the 4-hydroxytoremifene quinone methide reacts with two molecules of GSH and loses chlorine to give the corresponding di-GSH conjugates. The reaction mechanism likely involves an episulfonium ion intermediate which may contribute to the potential cytotoxic effects of toremifene. Similar to what was observed with 4-hydroxytamoxifen, 4-hydroxytoremifene was metabolized to di-GSH conjugates in microsomal incubations at about 3 times the rate of 4-hydroxytamoxifen, although no conjugates were detected with MCF-7 cells. Finally, these data suggest that quinone methide formation may not make a significant contribution to the cytotoxic and genotoxic effects of tamoxifen and toremifene.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Rui; Siegel, David; Ross, David, E-mail: david.ross@ucdenver.edu

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 NQO1more » 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.« less

Computational design of molecules for an all-quinone redox flow battery.

PubMed

Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

2015-02-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

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

Design and synthesis of novel isoxazole tethered quinone-amino Acid hybrids.

PubMed

Ravi Kumar, P; Behera, Manoranjan; 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.

QUINONE METHIDES IN LIGNIFICATION

USDA-ARS?s Scientific Manuscript database

Quinone methides play an important role in lignification. They are produced directly, as intermediates, when lignin monomers, be they hydroxycinnamyl alcohols, hydroxycinnamaldehydes, or hydroxycinnamates, couple or cross-couple at their 8-positions. A variety of post-coupling quinone methide rearom...

Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA.

PubMed

Fan, P W; Bolton, J L

2001-06-01

Despite the beneficial effects of tamoxifen in the treatment and prevention of breast cancer, long-term usage of this popular antiestrogen has been linked to an increased risk of developing endometrial cancer in women. One of the suggested pathways leading to the potential toxicity of tamoxifen involves its oxidative metabolism to 4-hydroxytamoxifen, which may be further oxidized to an electrophilic quinone methide. Alternatively, tamoxifen could undergo O-dealkylation to give cis/trans-1,2-diphenyl-1-(4-hydroxyphenyl)-but-1-ene, which is commonly known as metabolite E. Because of its structural similarity to 4-hydroxytamoxifen, metabolite E could also be biotransformed to a quinone methide, which has the potential to alkylate DNA and may contribute to the genotoxic effects of tamoxifen. To further probe the chemical reactivity/toxicity of such an electrophilic species, we have prepared metabolite E quinone methide chemically and enzymatically and examined its reactivity with glutathione (GSH) and DNA. Like 4-hydroxytamoxifen quinone methide, metabolite E quinone methide is quite stable; its half-life under physiological conditions is around 4 h, and its half-life in the presence of GSH is approximately 4 min. However, unlike the unstable GSH adducts of 4-hydroxytamoxifen quinone methide, metabolite E GSH adducts are stable enough to be isolated and characterized by NMR and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Reaction of metabolite E quinone methide with DNA generated exclusively deoxyguanosine adducts, which were characterized by LC/MS/MS. These data suggest that metabolite E has the potential to cause cytotoxicity/genotoxicity through the formation of a quinone methide.

Isoprenoid quinones resolve the stratification of microbial redox processes in a biogeochemical continuum from the photic zone to deep anoxic sediments of the Black Sea.

PubMed

Becker, Kevin W; Elling, Felix J; Schröder, Jan M; Lipp, Julius S; Goldhammer, Tobias; Zabel, Matthias; Elvert, Marcus; Overmann, Jörg; Hinrichs, Kai-Uwe

2018-03-09

The stratified water column of the Black Sea serves as a model ecosystem for studying the interactions of microorganisms with major biogeochemical cycles. Here we provide detailed analysis of isoprenoid quinones to study microbial redox processes in the ocean. In a continuum from the photic zone through the chemocline into deep anoxic sediments of the southern Black Sea, diagnostic quinones and inorganic geochemical parameters indicate niche segregation between redox processes and corresponding shifts in microbial community composition. Quinones specific for oxygenic photosynthesis and aerobic respiration dominate oxic waters, while quinones associated with thaumarchaeal ammonia-oxidation and bacterial methanotrophy, respectively, dominate a narrow interval in suboxic waters. Quinone distributions indicate highest metabolic diversity within the anoxic zone, with anoxygenic photosynthesis being a major process in its photic layer. In the dark anoxic layer, quinone profiles indicate occurrence of bacterial sulfur and nitrogen cycling, archaeal methanogenesis, and archaeal methanotrophy. Multiple novel ubiquinone isomers, possibly originating from unidentified intra-aerobic anaerobes, occur in this zone. The respiration modes found in the anoxic zone continue into shallow subsurface sediments, but quinone abundances rapidly decrease within the upper 50 cm below sea floor, reflecting the transition to lower energy availability. In the deep subseafloor sediments, quinone distributions and geochemical profiles indicate archaeal methanogenesis/methanotrophy and potentially bacterial fermentative metabolisms. We observed that sedimentary quinone distributions track lithology, which supports prior hypotheses that deep biosphere community composition and metabolisms are determined by environmental conditions during sediment deposition. Importance Microorganisms play crucial roles in global biogeochemical cycles. Yet, we have only a fragmentary understanding of the diversity of microorganisms and their metabolisms, as the majority remains uncultured. Thus, culture-independent approaches are critical for determining microbial diversity and active metabolic processes. In order to resolve the stratification of microbial communities in the Black Sea, we comprehensively analyzed redox process-specific isoprenoid quinone biomarkers in a unique continuous record from the photic zone through the chemocline into anoxic subsurface sediments. We describe an unprecedented quinone diversity that allowed us to detect distinct biogeochemical processes including oxygenic photosynthesis, archaeal ammonia oxidation, aerobic methanotrophy and anoxygenic photosynthesis in defined geochemical zones. Copyright © 2018 American Society for Microbiology.

Energetic and electronic computation of the two-hydrogen atom donation process in catecholic and non-catecholic anthocyanidins.

PubMed

Ali, Hussein M; Ali, Isra H

2018-03-15

Antioxidant activity of anthocyanidins is greatly affected by the 3-hydroxyl group and/or a catecholic moiety. The two-hydrogen atom donation process is frequently used to explain the high antioxidant activity of polyphenolic compounds leading to the formation of stable diketones e.g. 1,2-quinones. Thermodynamic parameters, HOMO and spin density were computed to identify the favoured path, either through the 3-hydroxyl group or through the catecholic moiety in a series of catecholic and non-catecholic 3-oxy- (and deoxy)-anthocyanidins. DFT calculations showed that the donation process in non-catecholic anthocyanidins depended on the substituents on ring B. Anthocyanidins with 3',5'-diOMe groups showed donation through 3,4'-OH or, otherwise, through 3,5-OH groups. Catecholic 3-oxyanthocyanidins, on the other hand, showed donation through the 3,4'-OH path rather than the catecholic path (4',3'-path). The 3,4'-path was favoured by the formation of planar 3-radicals in the first step and the stabilization of 4'-radicals in the second step by H-bonding with the 3'-OH group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanistic aspects of the tyrosinase oxidation of hydroquinone.

PubMed

Ramsden, Christopher A; Riley, Patrick A

2014-06-01

Contradictory reports on the behaviour of hydroquinone as a tyrosinase substrate are reconciled in terms of the ability of the initially formed ortho-quinone to tautomerise to the thermodynamically more stable para-quinone isomer. Oxidation of phenols by native tyrosinase requires activation by in situ formation of a catechol formed via an enzyme generated ortho-quinone. In the special case of hydroquinone, catechol formation is precluded by rapid tautomerisation of the ortho-quinone precursor to catechol formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4-naphthohydroquinone.

PubMed

Yuan, Xiu; Miller, Christopher J; Pham, A Ninh; Waite, T David

2014-06-01

Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH2Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5-7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH2Q increased with increasing pH and initial NH2Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ(2-), has been shown to be the reactive species with regard to the one-electron oxidation by O2 and comproportionation with the quinone species, both generating the semiquinone radical (NSQ(·-)). The oxidation of NSQ(·-) by O2 is shown to be the most important pathway for superoxide (O2(·-)) generation with a high intrinsic rate constant of 1.0×10(8)M(-1)s(-1). Both NSQ(·-) and O2(·-) served as chain-propagating species in the autoxidation of NH2Q. Cu(II) is capable of catalyzing the oxidation of NH2Q in the presence of O2 with the oxidation also accelerated by increasing the pH. Both the uncharged (NH2Q(0)) and the mono-anionic (NHQ(-)) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×10(4) and 1.2×10(7)M(-1)s(-1), respectively. The presence of O2 facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ(·-) resulting in the generation of O2(·-). The half-cell reduction potentials of various redox couples at neutral pH indicated good agreement between thermodynamic and kinetic considerations for various key reactions involved, further validating the proposed mechanisms involved in both the autoxidation and the copper-catalyzed oxidation of NH2Q in circumneutral pH solutions. Copyright © 2014 Elsevier Inc. All rights reserved.

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…

Changes of microbial population structure related to lignin degradation during lignocellulosic waste composting.

PubMed

Huang, Dan-Lian; Zeng, Guang-Ming; Feng, Chong-Ling; Hu, Shuang; Lai, Cui; Zhao, Mei-Hua; Su, Feng-Feng; Tang, Lin; Liu, Hong-Liang

2010-06-01

Microbial populations and their relationship to bioconversion during lignocellulosic waste composting were studied by quinone profiling. Nine quinones were observed in the initial composting materials, and 15 quinones were found in compost after 50days of composting. The quinone species Q-9(H2), Q-10 and Q-10(H2) which are indicative of certain fungi appeared at the thermophilic stage but disappeared at the cooling stage. Q-10, indicative of certain fungi, and MK-7, characteristic of certain bacteria, were the predominant quinones during the thermophilic stage and were correlated with lignin degradation at the thermophilic stage. The highest lignin degradation ratio (26%) and good cellulose degradation were found at the cooling stage and were correlated with quinones Q-9, MK-7 and long-chain menaquinones attributed to mesophilic fungi, bacteria and actinomycetes, respectively. The present findings will improve the understandings of microbial dynamics and roles in composting, which could provide useful references for development of composting technology. Copyright 2010. Published by Elsevier Ltd.

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 Central

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. PMID:23162467

Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds

PubMed Central

2013-01-01

Background Phenolic compounds are widely distributed in plant kingdom and constitute one of the most important classes of natural and synthetic antioxidants. In the present study fifty one natural and synthetic structurally variant phenolic, enolic and anilinic compounds were examined as antioxidants and radical scavengers against DPPH, hydroxyl and peroxyl radicals. The structural diversity of the used phenolic compounds includes monophenols with substituents frequently present in natural phenols e.g. alkyl, alkoxy, ester and carboxyl groups, besides many other electron donating and withdrawing groups, in addition to polyphenols with 1–3 hydroxyl groups and aminophenols. Some common groups e.g. alkyl, carboxyl, amino and second OH groups were incorporated in ortho, meta and para positions. Results SAR study indicates that the most important structural feature of phenolic compounds required to possess good antiradical and antioxidant activities is the presence of a second hydroxyl or an amino group in o- or p-position because of their strong electron donating effect in these positions and the formation of a stable quinone-like products upon two hydrogen-atom transfer process; otherwise, the presence of a number of alkoxy (in o or p-position) and /or alkyl groups (in o, m or p-position) should be present to stabilize the resulted phenoxyl radical and reach good activity. Anilines showed also similar structural feature requirements as phenols to achieve good activities, except o-diamines which gave low activity because of the high energy of the resulted 1,2-dimine product upon the 2H-transfer process. Enols with ene-1,2-diol structure undergo the same process and give good activity. Good correlations were obtained between DPPH inhibition and inhibition of both OH and peroxyl radicals. In addition, good correlations were obtained between DPPH inhibition and antioxidant activities in sunflower oil and liver homogenate systems. Conclusions In conclusion, the structures of good anti radical and antioxidant phenols and anilines are defined. The obtained good correlations imply that measuring anti DPPH activity can be used as a simple predictive test for the anti hydroxyl and peroxyl radical, and antioxidant activities. Kinetic measurements showed that strong antioxidants with high activity have also high reaction rates indicating that factors stabilizing the phenoxyl radicals lower also the activation energy of the hydrogen transfer process. PMID:23497653

Improvement of Pro-Oxidant Capacity of Protocatechuic Acid by Esterification

PubMed Central

Zeraik, Maria Luiza; Petrônio, Maicon S.; Coelho, Dyovani; Regasini, Luis Octavio; Silva, Dulce H. S.; da Fonseca, Luiz Marcos; Machado, Sergio A. S.; Bolzani, Vanderlan S.; Ximenes, Valdecir F.

2014-01-01

Pro-oxidant effects of phenolic compounds are usually correlated to the one-electron redox potential of the phenoxyl radicals. Here we demonstrated that, besides their oxidizability, hydrophobicity can also be a decisive factor. We found that esterification of protocatechuic acid (P0) provoked a profound influence in its pro-oxidant capacity. The esters bearing alkyl chains containing two (P2), four (P4) and seven (P7) carbons, but not the acid precursor (P0), were able to exacerbate the oxidation of trolox, α-tocopherol and rifampicin. This effect was also dependent on the catechol moiety, since neither gallic acid nor butyl gallate showed any pro-oxidant effects. A comparison was also made with apocynin, which is well-characterized regarding its pro-oxidant properties. P7 was more efficient than apocynin regarding co-oxidation of trolox. However, P7 was not able to co-oxidize glutathione and NADH, which are targets of the apocynin radical. A correlation was found between pro-oxidant capacity and the stability of the radicals, as suggested by the intensity of the peak current in the differential pulse voltammetry experiments. In conclusion, taking into account that hydroquinone and related moieties are frequently found in biomolecules and quinone-based chemotherapeutics, our demonstration that esters of protocatechuic acid are specific and potent co-catalysts in their oxidations may be very relevant as a pathway to exacerbate redox cycling reactions, which are usually involved in their biological and pharmacological mechanisms of action. PMID:25340774

The transformation of triclosan by laccase: Effect of humic acid on the reaction kinetics, products and pathway.

PubMed

Dou, Rong-Ni; Wang, Jing-Hao; Chen, Yuan-Cai; Hu, Yong-You

2018-03-01

This study systematically explored the effect of humic acid (HA) (as model of natural organic matter) on the kinetics, products and transformation pathway of triclosan (TCS) by laccase-catalyzed oxidation. It was found that TCS could be effectively transformed by laccase-catalysis, with the apparent second-order rate constant being 0.056 U -1 mL min -1 . HA inhibited the removal rate of TCS. HA-induced inhibition was negatively correlated with HA concentration in the range of 0-10 mg L -1 and pH-dependent from 3.5 to 9.5. FT-IR and 13 C NMR spectra showed a decrease of aromatic hydroxyl (phenolic) groups and an increase of aromatic ether groups, indicating the cross-linking of HA via C-O-C and C-N-C bonds during enzyme-catalyzed oxidation. Ten principle oxidative products, including two quinone-like products (2-chlorohydroquinone, 2-chloro-5-(2,4-dichlodichlorophenoxy)-(1,4)benzoquinone), one chlorinated phenol (2,4-dichlorophenol (2,4-DCP)), three dimers, two trimmers and two tetramers, were detected by gas chromatograghy/mass spectrometry (GC-MS) and high performance liquid chromatography/quadrupole time-of-flight/mass spectrometry (HPLC/Q-TOF/MS). The presence of HA induced significantly lesser generation of self-polymers and enhanced cross-coupling between HA and self-polymers via C-O-C, C-N-C and C-C coupling pathways. A plausible transformation pathway was proposed as follows: TCS was initially oxidized to form reactive phenoxyl radicals, which self-coupled to each other subsequently by C-C and C-O pathway, yielding self-polymers. In addition, the scission of ether bond was also observed. The presence of HA can promote scission of ether bond and further oxidation of phenoxyl radicals, forming hydroxylated or quinone-like TCS. This study shed light on the behavior of TCS in natural environment and engineered processes, as well provided a perspective for the water/wastewater treatment using enzyme-catalyzed oxidation techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time-resolved FT EPR and optical spectroscopy study on photooxidation of aliphatic alpha-amino acids in aqueous solutions; electron transfer from amino vs carboxylate functional group.

PubMed

Tarabek, Peter; Bonifacić, Marija; Beckert, Dieter

2006-06-08

Using time-resolved Fourier transform electron paramagnetic resonance, FT EPR, and optical spectroscopy, the photooxidation of glycine, alpha-alanine, alpha-aminoisobutyric acid, and model compounds beta-alanine, methylamine and sodium acetate, by excited triplets of anthraquinone-2,6-disulfonate dianion was studied in aqueous solutions in the pH range 5-13. Anthraquinone radical trianions showing strong emissive spin-polarization (CIDEP) were formed, indicating fast electron transfer from the quenchers to the spin-polarized quinone triplet as the primary reaction. None of the primary radicals formed upon one-electron oxidation of quenchers could be detected at the nanosecond time scale of FT EPR measurements because of their very fast transformation into secondary products. The latter were identified to be decarboxylated alpha-aminoalkyl radicals for alpha-amino acids anions and zwitterions, beta-aminoalkyl radicals for beta-alanine zwitterions, and methyl radicals for acetate anions; corresponding aminyl radicals were the first EPR detectable products from beta-alanine anions and methylamine. Thus, anthraquinone-2,6-disulfonate triplet can take an electron from both NH(2)- and -CO(2)(-) functional groups forming aminium ((+*)NH(2)-) and acyloxyl (-CO(2)(*)) radicals, respectively. Aminium radicals derived from beta-alanine anions and CH(3)-NH(2) stabilize by deprotonation into aminyl radicals, whereas these derived from alpha-amino acids anions are known to suffer ultrafast decarboxylation (tau approximately 10 ps). Analysis of the polarization patterns revealed that decarboxylation from acyloxyl radicals are considerably slower (ns < tau < 0.1 micros). Therefore, in the case of alpha-amino acids, the isoelectronic structures NH(2)-CR(2)-CO(2)(*) and (+*)NH(2)-CR(2)-CO(2)(-) probably do not constitute resonance mesomeric forms of one and the same species and the decarboxylation of aminium radicals is not preceded by the intramolecular carboxylate to amino group electron transfer. Absolute triplet quenching rate constants at zero ionic strength were in the range of 2 x 10(8) to 2 x 10(9) M(-1) s(-1) for R-NH(2) and 2 x 10(7) to 10(8) M(-1) s(-1) for R-CO(2)(-) type of electron donors, reflecting in principle their standard reduction potentials. The strengths of acids: (+)NH(3)-(*)CH(2), (+)NH(3)-(*)C(CH(3))H, and (+)NH(3)-(*)C(CH(3))(2), pK(a) <4, >6, and >7, respectively, were found to be remarkably strongly dependent on alpha-C substitution. The conjugate bases of these alpha-aminoalkyl radicals reduce anthraquinone-2,6-disulfonate dianion ground state with k(sec) = 3 x 10(9) M(-1) s(-1).

Exciplex formation and excited state deactivation of difluoroborondipyrromethene (Bodipy) dyads.

PubMed

Benniston, Andrew C; Copley, Graeme; Lemmetyinen, Helge; Tkachenko, Nikolai V

2010-06-07

Two series of geometrically-related dyads are discussed based on the difluoroborondipyrromethene (Bodipy) unit, and incorporating covalently attached hydroquinone/quinone groups. These units are anchored directly, or via a phenylene spacer, to the Bodipy core at the meso position in one series (BD-MHQ, BD-MQ, BD-MPHQ, BD-MPQ), but for the second series the attachment site is the 2-position (BD-SHQ, BD-SQ, BD-SPHQ, BD-SPQ). The compounds show various levels of fluorescence depending on the oxidation state of the appended group and the substitution pattern. In non-polar solvents such as toluene, diethyl ether and dichlorobenzene, the S(1) state deactivation of the Bodipy unit in BD-SPQ and BD-MPQ is dominated by (1, 3)exciplex formation, which has not been reported for Bodipy derivatives so far. In the latter molecule, the decay of the exciplex is divided between population of the Bodipy triplet state (13 %-21 %) and ground state reformation. This partitioning is not seen for the side-on substituted derivative, BD-SPQ, and only ground state reformation is observed following decay of the exciplex. This difference in behavior is explained by the radical-pair inter-system-crossing mechanism, which more effectively operates in BD-MPQ because of the orthogonality of the donor-acceptor units. In the more polar solvent CH(3)CN all the quinone derivatives show fast formation of the charge-separated state (k(CS)) followed by slower charge recombination (k(CR)). The ratio k(CS)/k(CR)

Ultrafast Adiabatic Photodehydration of 2-Hydroxymethylphenol and the Formation of Quinone Methide.

PubMed

Škalamera, Đani; Antol, Ivana; Mlinarić-Majerski, Kata; Vančik, Hrvoj; Phillips, David Lee; Ma, Jiani; Basarić, Nikola

2018-04-20

The photochemical reactivity of 2-hydroxymethylphenol (1) was investigated experimentally by photochemistry under cryogenic conditions, by detecting reactive intermediates by IR spectroscopy, and by using nanosecond and femtosecond transient absorption spectroscopic methods in solution at room temperature. In addition, theoretical studies were performed to facilitate the interpretation of the experimental results and also to simulate the reaction pathway to obtain a better understanding of the reaction mechanism. The main finding of this work is that photodehydration of 1 takes place in an ultrafast adiabatic photochemical reaction without any clear intermediate, delivering quinone methide (QM) in the excited state. Upon photoexcitation to a higher vibrational level of the singlet excited state, 1 undergoes vibrational relaxation leading to two photochemical pathways, one by which synchronous elimination of H 2 O gives QM 2 in its S 1 state and the other by which homolytic cleavage of the phenolic O-H bond produces a phenoxyl radical (S 0 ). Both are ultrafast processes that occur within a picosecond. The excited state of QM 2 (S 1 ) probably deactivates to S 0 through a conical intersection to give QM 2 (S 0 ), which subsequently delivers benzoxete 4. Elucidation of the reaction mechanisms for the photodehydration of phenols by which QMs are formed is important to tune the reactivity of QMs with DNA and proteins for the potential application of QMs in medicine as therapeutic agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Purification and Characterization of Pyranose Oxidase from the White Rot Fungus Trametes multicolor

PubMed Central

Leitner, Christian; Volc, Jindrich; Haltrich, Dietmar

2001-01-01

We purified an intracellular pyranose oxidase from mycelial extracts of the white rot fungus Trametes multicolor by using ammonium sulfate fractionation, hydrophobic interaction, ion-exchange chromatography, and gel filtration. The native enzyme has a molecular mass of 270 kDa as determined by equilibrium ultracentrifugation and is composed of four identical 68-kDa subunits as determined by matrix-assisted laser desorption ionization mass spectrometry. Each subunit contains one covalently bound flavin adenine dinucleotide as its prosthetic group. The enzyme oxidizes several aldopyranoses specifically at position C-2, and its preferred electron donor substrates are d-glucose, d-xylose, and l-sorbose. During this oxidation reaction electrons are transferred to oxygen, yielding hydrogen peroxide. In addition, the enzyme catalyzes the two-electron reduction of 1,4-benzoquinone, several substituted benzoquinones, and 2,6-dichloroindophenol, as well as the one-electron reduction of the ABTS [2,2′-azinobis(3-ethylbenzthiazolinesulfonic acid)] cation radical. As judged by the catalytic efficiencies (kcat/Km), some of these quinone electron acceptors are much better substrates for pyranose oxidase than oxygen. The optimum pH of the pyranose oxidase-catalyzed reaction depends strongly on the electron acceptor employed and varies from 4 to 8. It has been proposed that the main metabolic function of pyranose oxidase is as a constituent of the ligninolytic system of white rot fungi that provides peroxidases with H2O2. An additional function could be reduction of quinones, key intermediates that are formed during mineralization of lignin. PMID:11472941

The binding of quinone to the photosynthetic reaction centers: kinetics and thermodynamics of reactions occurring at the QB-site in zwitterionic and anionic liposomes.

PubMed

Mavelli, Fabio; Trotta, Massimo; Ciriaco, Fulvio; Agostiano, Angela; Giotta, Livia; Italiano, Francesca; Milano, Francesco

2014-07-01

Liposomes represent a versatile biomimetic environment for studying the interaction between integral membrane proteins and hydrophobic ligands. In this paper, the quinone binding to the QB-site of the photosynthetic reaction centers (RC) from Rhodobacter sphaeroides has been investigated in liposomes prepared with either the zwitterionic phosphatidylcholine (PC) or the negatively charged phosphatidylglycerol (PG) to highlight the role of the different phospholipid polar heads. Quinone binding (K Q) and interquinone electron transfer (L AB) equilibrium constants in the two type of liposomes were obtained by charge recombination reaction of QB-depleted RC in the presence of increasing amounts of ubiquinone-10 over the temperature interval 6-35 °C. The kinetic of the charge recombination reactions has been fitted by numerically solving the ordinary differential equations set associated with a detailed kinetic scheme involving electron transfer reactions coupled with quinone release and uptake. The entire set of traces at each temperature was accurately fitted using the sole quinone release constants (both in a neutral and a charge separated state) as adjustable parameters. The temperature dependence of the quinone exchange rate at the QB-site was, hence, obtained. It was found that the quinone exchange regime was always fast for PC while it switched from slow to fast in PG as the temperature rose above 20 °C. A new method was introduced in this paper for the evaluation of constant K Q using the area underneath the charge recombination traces as the indicator of the amount of quinone bound to the QB-site.

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

Anti-acne activities of pulsaquinone, hydropulsaquinone, and structurally related 1, 4-quinone derivatives.

PubMed

Cho, Soon-Chang; Sultan, Md Zakir; Moon, Surk-Sik

2009-04-01

Quinone type compound, pulsaquinone 1, isolated from the aqueous ethanol extract of the roots of Pulsatilla koreana exhibited antimicrobial activities against an anaerobic non-spore-forming gram-positive bacillus, Propionibacterium acnes, which is related with the pathogenesis of the inflamed lesions in a common skin disease, acne vulgaris. Compound 1 was unstable on standing and thus converted to more stable compound 2, namely hydropulsaquinone by hydrogenation, whose activity was comparable to mother compound 1 (MIC for 1 and 2 against P. acnes: 2.0 and 4.0 microg/mL, respectively). Other structurally-related quinone derivatives (3-13) were also tested for structure-activity relationship against anaerobic and aerobic bacteria, and fungi. The antimicrobial activity was fairly good when the quinone moiety was fused with a nonpolar 6- or 7-membered ring on the right side whether or not conjugated (1,4-naphtoquinone derivatives 3-5), while simple quinone compounds 6-9 showed poor activity. It seems that the methoxy groups at the left side of the quinone function deliver no considerable antimicrobial effect.

Bioinspired aerobic oxidation of secondary amines and nitrogen heterocycles with a bifunctional quinone catalyst.

PubMed

Wendlandt, Alison E; Stahl, Shannon S

2014-01-08

Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here we report a novel bioinspired quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts.

UV-Vis spectrophotometry of quinone flow battery electrolyte for in situ monitoring and improved electrochemical modeling of potential and quinhydrone formation.

PubMed

Tong, Liuchuan; Chen, Qing; Wong, Andrew A; Gómez-Bombarelli, Rafael; Aspuru-Guzik, Alán; Gordon, Roy G; Aziz, Michael J

2017-12-06

Quinone-based aqueous flow batteries provide a potential opportunity for large-scale, low-cost energy storage due to their composition from earth abundant elements, high aqueous solubility, reversible redox kinetics and their chemical tunability such as reduction potential. In an operating flow battery utilizing 9,10-anthraquinone-2,7-disulfonic acid, the aggregation of an oxidized quinone and a reduced hydroquinone to form a quinhydrone dimer causes significant variations from ideal solution behavior and of optical absorption from the Beer-Lambert law. We utilize in situ UV-Vis spectrophotometry to establish (a), quinone, hydroquinone and quinhydrone molar attenuation profiles and (b), an equilibrium constant for formation of the quinhydrone dimer (K QHQ ) ∼ 80 M -1 . We use the molar optical attenuation profiles to identify the total molecular concentration and state of charge at arbitrary mixtures of quinone and hydroquinone. We report density functional theory calculations to support the quinhydrone UV-Vis measurements and to provide insight into the dimerization conformations. We instrument a quinone-bromine flow battery with a Pd-H reference electrode in order to demonstrate how complexation in both the negative (quinone) and positive (bromine) electrolytes directly impacts measured half-cell and full-cell voltages. This work shows how accounting for electrolyte complexation improves the accuracy of electrochemical modeling of flow battery electrolytes.

Quinone-induced Enhancement of DNA Cleavage by Human Topoisomerase IIα: Adduction of Cysteine Residues 392 and 405†

PubMed Central

Bender, Ryan P.; Ham, Amy-Joan L.; Osheroff, Neil

2010-01-01

Several quinone-based metabolites of drugs and environmental toxins are potent topoisomerase II poisons. These compounds act by adducting the protein, and appear to increase levels of enzyme-DNA cleavage complexes by at least two potentially independent mechanisms. Treatment of topoisomerase IIα with quinones inhibits DNA religation, and blocks the N-terminal gate of the protein by crosslinking its two protomer subunits. It is not known whether these two effects result from quinone adduction to the same amino acid residue(s) in topoisomerase IIα or whether they are mediated by modification of separate residues. Therefore, the present study identified amino acid residues in human topoisomerase IIα that are modified by quinones and determined their role in the actions of these compounds as topoisomerase II poisons. Four cysteine residues were identified by mass spectrometry as sites of quinone adduction: cys170, cys392, cys405, and cys455. Mutations (cys–>ala) were individually generated at each position. Only mutations at cys392 or cys405 reduced sensitivity (~50% resistance) to benzoquinone. Top2αC392A and top2αC405A displayed faster rates (~2–fold) of DNA religation than wild-type topoisomerase IIα in the presence of the quinone. In contrast, as determined by DNA binding, protein clamp closing, and protomer crosslinking experiments, mutations at cys392 and cys405 did not affect the ability of benzoquinone to block the N-terminal gate of topoisomerase IIα. These findings indicate that adduction of cys392 and cys405 is important for the actions of quinones against the enzyme, and increases levels of cleavage complexes primarily by inhibiting DNA religation. PMID:17298034

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 Ltd. All rights reserved.

Bioinspired Aerobic Oxidation of Secondary Amines and Nitrogen Heterocycles with a Bifunctional Quinone Catalyst

PubMed Central

Wendlandt, Alison E.; Stahl, Shannon S.

2014-01-01

Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here, we report a novel bioinspired quinone catalyst system, consisting of 1,10-phenanthroline-5,6-dione/ZnI2, that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts. PMID:24328193

Reduction of estrogen-induced transformation of mouse mammary epithelial cells by N-acetylcysteine

PubMed Central

Venugopal, Divya; Zahid, Muhammad; Mailander, Paula C; Meza, Jane L.; Rogan, Eleanor G.; Cavalieri, Ercole L.; Chakravarti, Dhrubajyoti

2009-01-01

A growing number of studies indicate that breast cancer initiation is related to abnormal estrogen oxidation to form an excess of estrogen-3,4-quinones, which react with DNA to form depurinating adducts and induce mutations. This mechanism is often called estrogen genotoxicity. 4-catechol estrogens, precursors of the estrogen-3,4-quinones, were previously shown to account for most of the transforming and tumorigenic activity. We examined whether estrogen-induced transformation can be reduced by inhibiting the oxidation of a 4-catechol estrogen to its quinone. We demonstrate that E6 cells (a normal mouse epithelial cell line) can be transformed by a single treatment with a catechol estrogen or its quinone. The transforming activities of 4-hydroxyestradiol and estradiol-3,4-quinone were comparable. N-acetylcysteine, a common antioxidant, inhibited the oxidation of 4-hydroxyestradiol to the quinone and consequent formation of DNA adducts. It also drastically reduced estrogen-induced transformation of E6 cells. These results strongly implicate estrogen genotoxicity in mammary cell transformation. Since N-acetylcysteine is well-tolerated in clinical studies, it may be a promising candidate for breast cancer prevention. PMID:18226522

Contribution of Quinones and Ketones/Aldehydes to the Optical Properties of Humic Substances (HS) and Chromophoric Dissolved Organic Matter (CDOM).

PubMed

Del Vecchio, Rossana; Schendorf, Tara Marie; Blough, Neil V

2017-12-05

The molecular basis of the optical properties of chromophoric dissolved organic matter (CDOM) and humic substances (HS) remains poorly understood and yet to be investigated adequately. This study evaluates the relative contributions of two broad classes of carbonyl-containing compounds, ketones/aldehydes versus quinones, to the absorption and emission properties of a representative suite of HS as well as a lignin sample. Selective reduction of quinones to hydroquinones by addition of small molar excesses of dithionite to these samples under anoxic conditions produced small or negligible changes in their optical properties; however, when measurable, these changes were largely reversible upon exposure to air, consistent with the reoxidation of hydroquinones to quinones. With one exception, estimates of quinone content based on dithionite consumption by the HS under anoxic conditions were in good agreement with past electrochemical measurements. In contrast, reduction of ketones/aldehydes to alcohols employing excess sodium borohydride produced pronounced and largely, but not completely, irreversible changes in the optical properties. The results demonstrate that (aromatic) ketones/aldehydes, as opposed to quinones, play a far more prominent role in the optical absorption and emission properties of these HS, consistent with these moieties acting as the primary acceptors in charge-transfer transitions within these samples. As a method, anoxic dithionite titrations may further allow additional insight into the content and impact of quinones/hydroquinones on the optical properties of HS and CDOM.

Pyrrole Alkaloids with Potential Cancer Chemopreventive Activity Isolated from a Goji Berry-Contaminated Commercial Sample of African Mango

PubMed Central

2015-01-01

Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2–8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and 1H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample. PMID:24792835

Exploring Chemical Routes Relevant to the Toxicity of Paracetamol and Its meta-Analogue at a Molecular Level.

PubMed

Castañeda-Arriaga, Romina; Galano, Annia

2017-06-19

Several chemical routes related to the toxicity of paracetamol (APAP, also known as acetaminophen), its analogue N-acetyl-m-aminophenol (AMAP), and their deacetylated derivatives, were investigated using the density functional theory. It was found that AMAP is more resilient to chemical oxidation than APAP. The chemical degradation of AMAP into radical intermediates is predicted to be significant only when it is induced by strong oxidants. This might explain the apparent contradictions among experimental evidence regarding AMAP toxicity. All of the investigated species are incapable of oxidizing DNA, but they can damage lipids by H atom transfer (HAT) from the bis-allylic site, with the phenoxyl radical of AMAP being the most threatening to the lipids' chemical integrity. Regarding protein damage, Cys residues were identified as the most likely targets. The damage in this case may involve two different routes: (i) HAT from the thiol site by phenoxyl radicals and (ii) protein arylation by the quinone imine (QI) derivatives. Both are not only thermochemically viable, but also are very fast reactions. According to the mechanism identified here as the most likely one for protein arylation, a rather large concentration of QI would be necessary for this damage to be significant. This might explain why APAP is nontoxic in therapeutic doses, while overdoses can result in hepatic toxicity. In addition, the QI derived from both APAP and AMAP were found to be capable of inflicting this kind of damage. In addition, it is proposed that they might increase • OH production via the Fenton reaction, which would contribute to their toxicity.

Photolysis of polycyclic aromatic hydrocarbons (PAHs) on Fe3+-montmorillonite surface under visible light: Degradation kinetics, mechanism, and toxicity assessments.

PubMed

Zhao, Song; Jia, Hanzhong; Nulaji, Gulimire; Gao, Hongwei; Wang, Fu; Wang, Chuanyi

2017-10-01

Photochemical behavior of various polycyclic aromatic hydrocarbons (PAHs) on Fe 3+ -modified montmorillonite was explored to determine their potential kinetics, pathways, and mechanism under visible light. Depending on the type of PAH molecules, the transformation rate follows the order of benzo[a]pyrene ≈ anthracene > benzo[a]anthracene > phenanthrene. Quantum simulation results confirm the crucial role of "cation-π" interaction between Fe 3+ and PAHs on their transformation kinetics. Primary intermediates, including quinones, ring-opening products and benzene derivatives, were identified by gas chromatography-mass spectrometer (GC-MS), and the possible photodegradation pathway of benzo[a]pyrene was proposed. Meanwhile, radical intermediates, such as reactive oxygen species (ROS) and free organic radicals, were detected by electron paramagnetic resonance (EPR) technique. The photolysis of selected PAHs, such as anthracene and benzo[a]pyrene, on clay surface firstly occurs by electron transfer from PAHs to Fe 3+ -montmorillonite, followed by degradation involving photo-induced ROS such as ·OH and ·O 2 - . To investigate the acute toxicity of photolysis products, the Microtox ® toxicity test was performed during the photodegradation processes of various PAHs. As a result, the photo-irradiation initially induces increased toxicity by generating reactive intermediates, such as free organic radicals, and then the toxicity gradually decreases with increasing of reaction time. Overall, the present study provides useful information to understand the fate and photo-transformation of PAHs in contaminated soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

Photographic fixative poisoning

MedlinePlus

Photographic developer poisoning; Hydroquinone poisoning; Quinone poisoning; Sulfite poisoning ... Poisonous ingredients include: Hydroquinones Quinones Sodium ... fixative can also break down (decompose) to form sulfur dioxide ...

Phototransformation of anthraquinone-2-sulphonate in aqueous solution.

PubMed

Bedini, Andrea; De Laurentiis, Elisa; Sur, Babita; Maurino, Valter; Minero, Claudio; Brigante, Marcello; Mailhot, Gilles; Vione, Davide

2012-09-01

Anthraquinone-2-sulphonate (AQ2S) is a triplet sensitiser that has recently been used to model the photoreactivity of chromophoric dissolved organic matter (CDOM). We show that the photolysis quantum yield of AQ2S under UVA irradiation varies from (3.4 ± 0.2) × 10(-3) at μM AQ2S levels to (1.8 ± 0.1) × 10(-2) at 3 mM AQ2S (μ±σ). This trend is consistent with a combination of direct phototransformation and transformation sensitised by a photogenerated reactive species. In both cases a transient water adduct of AQ2S would be involved. Depending on the initial quinone concentration, the adduct could undergo transformation, give back ground-state AQ2S or react with it. The prevalence of the latter process at high AQ2S concentration would account for the increased values of the photolysis quantum yield. When using AQ2S as a triplet sensitiser, one should not exceed an initial concentration of 0.1 mM. Under the latter conditions the sensitised process is negligible compared to the direct photolysis, providing a simpler system to be studied, and the photolysis quantum yield is independent of the initial AQ2S concentration. This paper also shows, by adoption of density functional theory calculations, that the triplet state of AQ2S has most of the spin density localised on C[double bond, length as m-dash]O, analogous to other photoactive quinones, which accounts for the oxidising character of the triplet state that tends to be reduced to a semiquinone radical.

Regiocontrol by remote substituents. An enantioselective total synthesis of frenolicin B via a highly regioselective Diels-Alder reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraus, G.A.; Li, J.; Gordon, M.S.

1993-06-30

The quinone subunit is contained in a broad range of biologically important natural products such as frenolicin B, which is a member of the pyranonaphthoquinone family. The diverse biological activity of quinones has led to the development of several new synthetic methods for quinones. Among the pathways featuring a cycloaddition reaction, one of the most general methods for the regiospecific synthesis of substituted quinones was pioneered by H.J. Rapoport and others. This method involves the Diels-Alder reaction of a substituted quinone. As part of a program to evaluate the directing effects of functional groups not directly attached to the atomsmore » undergoing Diels-Alder cycloaddition, we now report that remote substituents on a dienophile can confer excellent regioselectivity in Diels-Alder reactions. This work has led to an extremely direct synthesis of the pyranonaphthoquinone framework and to the first synthesis of frenolicin B (1). 19 refs., 1 fig.« less

An x-ray absorption study of the iron site in bacterial photosynthetic reaction centers.

PubMed Central

Bunker, G; Stern, E A; Blankenship, R E; Parson, W W

1982-01-01

Measurements were made of the extended x-ray absorption fine structure (EXAFS) of the iron site in photosynthetic reaction centers from the bacterium Rhodopseudomonas sphaeroides. Forms with two quinones, two quinones with added o-phenanthroline, and one quinone were studied. Only the two forms containing two quinones maintained their integrity and were analyzed. The spectra show directly that the added o-phenanthroline does not chelate the iron atom. Further analysis indicates that the iron is octahedrally coordinated by nitrogen and/or oxygen atoms located at various distances, with the average value of about 2.14 A. The analysis suggests that most of the ligands are nitrogens and that three of the nitrogen ligands belong to histidine rings. This interpretation accounts for several unusual features of the EXAFS spectrum. We speculate that the quinones are bound to the histidine rings in some manner. Qualitative features of the absorption edge spectra also are discussed and are related to the Fe-ligand distance. PMID:6977382

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

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.

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.

All three quinone species play distinct roles in ensuring optimal growth under aerobic and fermentative conditions in E. coli K12

PubMed Central

Nitzschke, Annika

2018-01-01

The electron transport chain of E. coli contains three different quinone species, ubiquinone (UQ), menaquinone (MK) and demethylmenaquinone (DMK). The content and ratio of the different quinone species vary depending on the external conditions. To study the function of the different quinone species in more detail, strains with deletions preventing UQ synthesis, as well as MK and/or DMK synthesis were cultured under aerobic and anaerobic conditions. The strains were characterized with respect to growth and product synthesis. As quinones are also involved in the control of ArcB/A activity, we analyzed the phosphorylation state of the response regulator as well as the expression of selected genes.The data show reduced aerobic growth coupled to lactate production in the mutants defective in ubiquinone synthesis. This confirms the current assumption that ubiquinone is the main quinone under aerobic growth conditions. In the UQ mutant strains the amount of MK and DMK is significantly elevated. The strain synthesizing only DMK is less affected in growth than the strain synthesizing MK as well as DMK. An inhibitory effect of MK on aerobic growth due to increased oxidative stress is postulated.Under fermentative growth conditions the mutant synthesizing only UQ is severely impaired in growth. Obviously, UQ is not able to replace MK and DMK during anaerobic growth. Mutations affecting quinone synthesis have an impact on ArcA phosphorylation only under anaerobic conditions. ArcA phosphorylation is reduced in strains synthesizing only MK or MK plus DMK. PMID:29614086

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Hui; Shi, Qiong; Song, Xiufang

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 observedmore » 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.« less

Soda-amine pulping : reaction of amines with free phenolic [beta]-[omicron]-4 ethers

Treesearch

John R. Obst

1981-01-01

The quinone methide from guaiacylglycol-ß-guaiacyl ether underwent nucleophilic addition to the a-carbon with primary and secondary amines at 40°C. At pulping temperature, 170°C, only the primary amine adduct was detected. The quinone methide from guaiacylglycerol-ß-guaiacyl ether gave analogous adducts at 40°C, but no quinone methide-amine adducts were detected at 170...

Strongly enhanced Fenton degradation of organic pollutants by cysteine: An aliphatic amino acid accelerator outweighs hydroquinone analogues.

PubMed

Li, Tuo; Zhao, Zhenwen; Wang, Quan; Xie, Pengfei; Ma, Jiahai

2016-11-15

Quinone-hydroquinone analogues have been proven to be efficient promoters of Fenton reactions by accelerating the Fe(III)/Fe(II) redox cycle along with self-destruction. However, so far there is little information on non-quinone-hydroquinone cocatalyst for Fenton reactions. This study found that cysteine, a common aliphatic amino acid, can strongly enhance Fenton degradation of organic pollutants by accelerating Fe(III)/Fe(II) redox cycle, as quinone-hydroquinone analogues do. Further, cysteine is superior to quinone-hydroquinone analogues in catalytic activity, H 2 O 2 utilization and atmospheric limits. The cocatalysis mechanism based on the cycle of cysteine/cystine was proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo exposure of Dreissena polymorpha mussels to the quinones menadione and lawsone: menadione is more toxic to mussels than lawsone.

PubMed

Osman, A M; Rotteveel, S; den Besten, P J; van Noort, P C M

2004-01-01

The principal aim of this study was to assess whether the two quinones, menadione (2-methyl-1,4-naphthoquinone) and lawsone (2-hydroxy-1,4-naphthoquinone), elicit differential toxicity in mussels as has been reported for higher organisms. Therefore, the effects of short-term (48 h) and long-term (20 days) exposure of the two quinones at concentrations of 0.56 and 1 mg l(-1) to zebra mussels, Dreissena polymorpha, under laboratory conditions were studied. After the short-term exposure, the specific activities of the two-electron quinone oxidoreductase (DT-diaphorase) and the one-electron catalysing quinone reductases NADPH-cytochrome c reductase and NADH-cytochrome c reductase were determined in the gills and the rest of the soft tissues (soft mussel tissues minus the gills) of both treated and control mussels. At the higher concentrations of menadione and lawsone used, a significant reduction of the activity of NADPH-cytochrome c reductase in the gills and in the rest of the soft mussel tissues (by 33-34% and 31-43%, respectively) was observed. The activities of DT-diaphorase and NADH-cytochrome c reductase were not significantly affected. Interestingly, DT-diaphorase was observed in the gills, an organ requiring protection against antioxidants. Furthermore, a single-cell electrophoretic assay (comet assay) performed with gill cells to assess DNA damage by the quinones did not show any significant difference between the treated and the control organisms. This indicates that the formation of reactive species by the quinone metabolism in vivo in the mussels was possibly suppressed through the concerted action of DT-diaphorase and antioxidant enzymes. The results of in vitro experiments with gill extracts confirmed the protective role of DT-diaphorase. The rate of the two-electron quinone reduction was found to be five times that of the one-electron quinone reduction. The results of the long-term exposure unambiguously demonstrated that in mussels menadione, unlike in higher organisms, is more toxic than lawsone. The lack of detectability of xanthine oxidase in the mussel tissues could explain the comparatively lower toxicity of lawsone in the invertebtrate, lending support to a previous suggestion that xanthine oxidase might be responsible for the mechanism of toxicity of lawsone in higher organisms in vivo. Copyright 2004 John Wiley & Sons, Ltd.

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 Q A and Q B sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q B 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 Q A and Q B 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 Q A–Q B– biradical and competitive binding assays.« less

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

PubMed

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

2015-03-31

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, we have investigated and characterized the interactions of the protein with the quinones in the Q(A) and Q(B) sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q(B) 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 Q(A) and Q(B) sites. 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 Q(A)⁻Q(B)⁻ biradical and competitive binding assays.

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.

Transformation of Flame Retardant Tetrabromobisphenol A by Aqueous Chlorine and the Effect of Humic Acid.

PubMed

Gao, Yuan; Pang, Su-Yan; Jiang, Jin; Ma, Jun; Zhou, Yang; Li, Juan; Wang, Li-Hong; Lu, Xue-Ting; Yuan, Li-Peng

2016-09-06

In this work, it was found that the most widely used brominated flame retardant tetrabromobisphenol A (TBrBPA) could be transformed by free chlorine over a wide pH range from 5 to 10 with apparent second-order rate constants from 138 to 3210 M(-1)·s(-1). A total of eight products, including one quinone-like compound (i.e., 2,6-dibromoquinone), two dimers, and several simple halogenated phenols (e.g., 4-(2-hydroxyisopropyl)-2,6-dibromophenol, 2,6-dibromohydroquinone, and 2,4,6-tribromophenol), were detected by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) using a novel precursor ion scan (PIS) approach. A tentative reaction pathway was proposed: chlorine initially oxidized TBrBPA leading to the formation of a phenoxy radical, and then this primary radical and its secondary intermediates (e.g., 2,6-dibromo-4-isopropylphenol carbocation) formed via beta-scission subsequently underwent substitution, dimerization, and oxidation reactions. Humic acid (HA) considerably inhibited the degradation rates of TBrBPA by chlorine even accounting for oxidant consumption. A similar inhibitory effect of HA was also observed in permanganate and ferrate oxidation. This inhibitory effect was possibly attributed to the fact that HA competitively reacted with the phenoxy radical of TBrBPA and reversed it back to parent TBrBPA. This study confirms that chlorine can transform phenolic compounds (e.g., TBrBPA) via electron transfer rather than the well-documented electrophilic substitution, which also have implications on the formation pathway of halo-benzoquinones during chlorine disinfection. These findings can improve the understanding of chlorine chemistry in water and wastewater treatment.

Extracellular degradation of tetrabromobisphenol A via biogenic reactive oxygen species by a marine Pseudoalteromonas sp.

PubMed

Gu, Chen; Wang, Jing; Guo, Mengfan; Sui, Meng; Lu, Hong; Liu, Guangfei

2018-06-07

Tetrabromobisphenol A (TBBPA) has attracted considerable attention due to its ubiquitous presence in different environmental compartments worldwide. However, information on its aerobic biodegradability in coastal environments remains unknown. Here, the aerobic biodegradation of TBBPA using a Pseudoalteromonas species commonly found in the marine environment was investigated. We found that extracellular biogenic siderophore, superoxide anion radical (O 2 •- ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( • OH) were involved in TBBPA degradation. Upregulation of genes (nqrA and lodA) encoding Na + -translocating NADH-quinone oxidoreductase and l-lysine-ε-oxidase supported the extracellular O 2 •- and H 2 O 2 production. The underlying mechanism of TBBPA biodegradation presumably involves both O 2 •- reduction and • OH-based advanced oxidation process (AOP). Furthermore, TBBPA intermediates of tribromobisphenol A, 4-isopropylene-2,6-dibromophenol, 4-(2-hydroxyisopropyl)-2,6-dibromophenol, 2,4,6-tribromophenol (TBP), 4-hydroxybenzoic acid, and 2-bromobenzoic acid were detected in the culture medium. Debromination and β-scission pathways of TBBPA biodegradation were proposed. Additionally, membrane integrity assays revealed that the increase of intracellular catalase (CAT) activity and the extracellular polymeric substances (EPS) might account for the alleviation of oxidative damage. These findings could deepen understanding of the biodegradation mechanism of TBBPA and other related organic pollutants in coastal and artificial bioremediation systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Involvement of superoxide radical in extracellular ferric reduction by iron-deficient bean roots. [Phadeolus vulgaris L. var Prelude

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cakmak, I.; van de Wetering, D.A.M.; Marschner, H.

The recent proposal of Tipton and Thowsen that iron-deficient plants reduce ferric chelates in cell walls by a system dependent on the leakage of malate from root cells was tested. Results are presented showing that this mechanism could not be responsible for the high rates of ferric reduction shown by roots of iron-deficient bean (Phaseolus vulgaris L. var Prelude) plants. The role of O/sub 2/ in the reduction of ferric chelates by roots of iron-deficient bean plants was also tested. The rate of Fe(III) reduction was the same in the presence and in the absence of O/sub 2/. However, inmore » the presence of O/sub 2/ the reaction was partially inhibited by superoxide dismutase (SOD), which indicates a role for the superoxide radical, O/sub 2//sup -/, as a facultative intermediate electron carrier. The inhibition by SOD increased with substrate pH and with decrease in concentration of the ferrous scavenger bathophenanthroline-disulfonate. The results are consistent with a mechanism for transmembrane electron in which a flavin or quinone is the final electron carrier in the plasma membrane. The results are discussed in relation to the ecological importance that O/sub 2//sup -/ may have in the acquisition of ferric iron by dicotyledonous plants.« less

Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radogna, Flavia; Paternoster, Laura; Istitututo di Chimica Biologica, Universita di Urbino Carlo Bo

Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not leadmore » to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.« less

Clinical physiology and mechanism of dizocilpine (MK-801): electron transfer, radicals, redox metabolites and bioactivity.

PubMed

Kovacic, Peter; Somanathan, Ratnasamy

2010-01-01

Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3'-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and ant-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties.

The Formation of Organic Compounds of Astrobiological Interest by the Irradiation Processing of Astrophysical Ices

NASA Technical Reports Server (NTRS)

Sandford, Scott A.

2015-01-01

Many environments in space contain very low temperature mixed molecular ices that are exposed to ionizing radiation in the form of cosmic rays and high-energy photons. While traditional chemistry would not be expected to occur at the temperatures typical of these ices (T < 50 K), ionizing radiation can break bonds in the original molecules in the ices to form highly reactive ions and radicals. These ions and radicals are subsequently free to react despite the low temperatures of the original ices. Laboratory experiments, many of them carried out at the Astrochemistry Laboratory at NASA-Ames, show that the irradiation of ices made of even simple molecules like H2O, CO, CO2, CH4, NH3, etc. can result in the robust formation of large numbers of far more complex organic compounds. Many of these new products are of direct interest to astrobiology. For example, the irradiation of mixed molecular ices has been shown to produce amino acids, amphiphiles, quinones, sugars, heterocyclic compounds, and nucleobases, all molecular building blocks used by terrestrial life. Insofar as the presence of these materials plays a role in the origin of life on planets, this has profound implications for the potential abundance of life in the universe since these experiments simulate universal conditions that are expected to be found wherever new stars and planets form.

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.

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.

Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

PubMed

Palan, Prabhudas R; Woodall, Angela L; Anderson, Patrick S; Mikhail, Magdy S

2004-05-01

alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.

Potential Metabolic Activation of a Representative C2-Alkylated Polycyclic Aromatic Hydrocarbon 6-Ethylchrysene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells

PubMed Central

2016-01-01

Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills. PMID:27054409

Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties.

PubMed

Azam, S; Hadi, N; Khan, N U; Hadi, S M

2004-10-01

It is believed that anticancer and apoptosis inducing properties of green tea are mediated by it's polyphenolic constituents particularly catechins. A number of reports have shown that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is among the most effective chemopreventive and apoptosis-inducing agents present in the beverage. Plant polyphenols are naturally occurring antioxidants but they also exhibit prooxidant properties. Over the last several years we have shown that various classes of plant polyphenols including flavonoids, curcuminoids and tannins are capable of catalyzing oxidative DNA cleavage particularly in the presence of transition metal ions such as copper and iron. With a view to understand the chemical basis of various pharmacological properties of green tea, in this paper we have compared the prooxidant properties of green tea polyphenols--EGCG and EC ((-)-epicatechin). The rate of oxidative DNA degradation as well as hydroxyl radical and superoxide anion formation was found to be greater in the case of EGCG as compared with EC. It was also shown that copper mediated oxidation of EC and EGCG possibly leads to the formation of polymerized polyphenols. Further, it was indicated that copper oxidized catechins were more efficient prooxidants as compared with their unoxidized forms. These results correlate with the observation by others that EGCG is the most effective apoptosis inducing polyphenol present in green tea. They are also in support of our hypothesis that prooxidant action of plant polyphenols may be an important mechanism of their anticancer properties. A model for binding of Cu(II) to EC has been presented where the formation of quinone and a quinone methide has been proposed.

Copper increases the ability of 6-hydroxydopamine to generate oxidative stress and the ability of ascorbate and glutathione to potentiate this effect: potential implications in Parkinson's disease.

PubMed

Cruces-Sande, Antón; Méndez-Álvarez, Estefanía; Soto-Otero, Ramón

2017-06-01

Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals. In this study, we examined the effects induced by copper on 6-OHDA autoxidation. Our data show that both Cu + and Cu 2+ caused an increase in • OH production by 6-OHDA autoxidation, which was accompanied by an increase in the rate of both p-quinone formation and H 2 O 2 accumulation. The presence of ascorbate greatly enhanced this process by establishing a redox cycle which regenerates 6-OHDA from its p-quinone. However, the presence of glutathione did not change significantly the copper-induced effects. We observed that copper is able to potentiate the ability of 6-OHDA to cause both lipid peroxidation and protein oxidation, with the latter including a reduction in free-thiol content and an increase in carbonyl content. Ascorbate also increases the lipid peroxidation induced by the action of copper and 6-OHDA. Glutathione protects against the copper-induced lipid peroxidation, but does not reduce its potential to oxidize free thiols. These results clearly demonstrate the potential of copper to increase the capacity of 6-OHDA to generate oxidative stress and the ability of ascorbate to enhance this potential, which may contribute to the destruction of dopaminergic neurons. © 2017 International Society for Neurochemistry.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quinlan, Jason; Xu, Feng; Sweeney, Matthew

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.

Isoprenoid quinones of the genus Legionella.

PubMed Central

Karr, D E; Bibb, W F; Moss, C W

1982-01-01

Representative strains of each of the named species of Legionella were examined for isoprenoid quinones by reverse-phase thin-layer chromatography. All strains contained three or more ubiquinones (Q9, Q10, Q11, Q12, Q13) which were useful for placing the species into one of three distinct groups. Group 1 contained L. longbeachae, L. bozemanii, L. dumoffi, and L. gormanii; group 2 contained only L. micdadei; and group 3 contained only L. pneumophila. The identities of the quinones were established by UV spectroscopy and mass spectrometry. PMID:7107837

Quinone-induced protein modifications: Kinetic preference for reaction of 1,2-benzoquinones with thiol groups in proteins.

PubMed

Li, Yuting; Jongberg, Sisse; Andersen, Mogens L; Davies, Michael J; Lund, Marianne N

2016-08-01

Oxidation of polyphenols to quinones serves as an antioxidative mechanism, but the resulting quinones may induce damage to proteins as they react through a Michael addition with nucleophilic groups, such as thiols and amines to give protein adducts. In this study, rate constants for the reaction of 4-methylbenzoquinone (4MBQ) with proteins, thiol and amine compounds were determined under pseudo first-order conditions by UV-vis stopped-flow spectrophotometry. The chemical structures of the adducts were identified by LC-ESI-MS/MS. Proteins with free thiols were rapidly modified by 4MBQ with apparent second order rate constants, k2 of (3.1±0.2)×10(4)M(-1)s(-1) for bovine serum albumin (BSA) and (4.8±0.2)×10(3)M(-1)s(-1) for human serum albumin at pH 7.0. These values are at least 12-fold greater than that for α-lactalbumin (4.0±0.2)×10(2)M(-1)s(-1), which does not contain any free thiols. Reaction of Cys-34 of BSA with N-ethylmaleimide reduced the thiol concentration by ~59%, which resulted in a decrease in k2 by a similar percentage, consistent with rapid adduction at Cys-34. Reaction of 4MBQ with amines (Gly, Nα-acetyl-l-Lys, Nε-acetyl-l-Lys and l-Lys) and the guanidine group of Nα-acetyl-l-Arg was at least 5×10(5) slower than with low-molecular-mass thiols (l-Cys, Nα-acetyl-l-Cys, glutathione). The thiol-quinone interactions formed colorless thiol-phenol products via an intermediate adduct, while the amine-quinone interactions generated colored amine-quinone products that require oxygen involvement. These data provide strong evidence for rapid modification of protein thiols by quinone species which may be of considerable significance for biological and food systems. Copyright © 2016 Elsevier Inc. All rights reserved.

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 )

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 R ² higher than 0.94. The BHandHLYP functional presented the best fit to the experimental values ( R ² = 0.957), followed by M06-2x ( R ² = 0.947) and PBE0 ( R ² = 0.942).

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.

Characterizing chlorine oxidation of dissolved organic matter and disinfection by-product formation with fluorescence spectroscopy and parallel factor analysis

NASA Astrophysics Data System (ADS)

Beggs, Katherine M. H.; Summers, R. Scott; McKnight, Diane M.

2009-12-01

Relationships between chlorine demand and disinfection by-product (DBP) formation during chlorination and fluorescence of dissolved organic matter (DOM) were developed. Fluorescence excitation and emission (EEM) spectroscopy was employed, and parameters including fluorescence index, redox index, and overall fluorescence intensity (OFI) were correlated to chlorine demand and DBP formation. The EEMs were also analyzed using a well established global parallel factor analysis (PARAFAC) model which resolves the fluorescence signal into 13 components, including quinone-like and protein-like components. Over an 8-day chlorination period the OFI and sum of the 13 PARAFAC loadings decreased by more than 70%. The remaining identified quinone-like compounds within the DOM were shifted to a more oxidized state. Quinone fluorescence was strongly correlated to both reduced fluorescence intensity and to chlorine demand which indicates that fluorescence may be used to track the chlorine oxidation of DOM. Quinone fluorescence was also correlated strongly with both classes of regulated DBPs: total trihalomethanes and haloacetic acids. Quinone-like components were found to be strongly correlated to overall, short-term, and long-term specific DBP formation. The results of this study show that fluorescence is a useful tool in tracking both DOM oxidation and DBP formation during chlorination.

High-capacity aqueous zinc batteries using sustainable quinone electrodes

PubMed Central

Zhao, Qing; Huang, Weiwei; Luo, Zhiqiang; Liu, Luojia; Lu, Yong; Li, Yixin; Li, Lin; Hu, Jinyan; Ma, Hua; Chen, Jun

2018-01-01

Quinones, which are ubiquitous in nature, can act as sustainable and green electrode materials but face dissolution in organic electrolytes, resulting in fast fading of capacity and short cycle life. We report that quinone electrodes, especially calix[4]quinone (C4Q) in rechargeable metal zinc batteries coupled with a cation-selective membrane using an aqueous electrolyte, exhibit a high capacity of 335 mA h g−1 with an energy efficiency of 93% at 20 mA g−1 and a long life of 1000 cycles with a capacity retention of 87% at 500 mA g−1. The pouch zinc batteries with a respective depth of discharge of 89% (C4Q) and 49% (zinc anode) can deliver an energy density of 220 Wh kg−1 by mass of both a C4Q cathode and a theoretical Zn anode. We also develop an electrostatic potential computing method to demonstrate that carbonyl groups are active centers of electrochemistry. Moreover, the structural evolution and dissolution behavior of active materials during discharge and charge processes are investigated by operando spectral techniques such as IR, Raman, and ultraviolet-visible spectroscopies. Our results show that batteries using quinone cathodes and metal anodes in aqueous electrolyte are reliable approaches for mass energy storage. PMID:29511734

High-capacity aqueous zinc batteries using sustainable quinone electrodes.

PubMed

Zhao, Qing; Huang, Weiwei; Luo, Zhiqiang; Liu, Luojia; Lu, Yong; Li, Yixin; Li, Lin; Hu, Jinyan; Ma, Hua; Chen, Jun

2018-03-01

Quinones, which are ubiquitous in nature, can act as sustainable and green electrode materials but face dissolution in organic electrolytes, resulting in fast fading of capacity and short cycle life. We report that quinone electrodes, especially calix[4]quinone (C4Q) in rechargeable metal zinc batteries coupled with a cation-selective membrane using an aqueous electrolyte, exhibit a high capacity of 335 mA h g -1 with an energy efficiency of 93% at 20 mA g -1 and a long life of 1000 cycles with a capacity retention of 87% at 500 mA g -1 . The pouch zinc batteries with a respective depth of discharge of 89% (C4Q) and 49% (zinc anode) can deliver an energy density of 220 Wh kg -1 by mass of both a C4Q cathode and a theoretical Zn anode. We also develop an electrostatic potential computing method to demonstrate that carbonyl groups are active centers of electrochemistry. Moreover, the structural evolution and dissolution behavior of active materials during discharge and charge processes are investigated by operando spectral techniques such as IR, Raman, and ultraviolet-visible spectroscopies. Our results show that batteries using quinone cathodes and metal anodes in aqueous electrolyte are reliable approaches for mass energy storage.

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

Electrochemistry coupled to (LC-)MS for the simulation of oxidative biotransformation reactions of PAHs.

PubMed

Wigger, Tina; Seidel, Albrecht; Karst, Uwe

2017-06-01

Electrochemistry coupled to liquid chromatography and mass spectrometry was used for simulating the biological and environmental fate of polycyclic aromatic hydrocarbons (PAHs) as well as for studying the PAH degradation behavior during electrochemical remediation. Pyrene and benzo[a]pyrene were selected as model compounds and oxidized within an electrochemical thin-layer cell equipped with boron-doped diamond electrode. At potentials of 1.2 and 1.6 V vs. Pd/H 2 , quinones were found to be the major oxidation products for both investigated PAHs. These quinones belong to a large group of PAH derivatives referred to as oxygenated PAHs, which have gained increasing attention in recent years due to their high abundance in the environment and their significant toxicity. Separation of oxidation products allowed the identification of two pyrene quinone and three benzo[a]pyrene quinone isomers, all of which are known to be formed via photooxidation and during mammalian metabolism. The good correlation between electrochemically generated PAH quinones and those formed in natural processes was also confirmed by UV irradiation experiments and microsomal incubations. At potentials higher than 2.0 V, further degradation of the initial oxidation products was observed which highlights the capability of electrochemistry to be used as remediation technique. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

PubMed

Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

2015-01-01

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

Melatonin in Apples and Juice: Inhibition of Browning and Microorganism Growth in Apple Juice.

PubMed

Zhang, Haixia; Liu, Xuan; Chen, Ting; Ji, Yazhen; Shi, Kun; Wang, Lin; Zheng, Xiaodong; Kong, Jin

2018-02-27

Synthetic melatonin ( N -acetyl-5-methoxytryptamine, MT) is popular in the US and Asian markets as a health supplement. Here, we identified a naturally occurring melatonin source in apple juice. Melatonin was present in all 18 apple cultivars tested. The highest melatonin level of the edible part of apple was detected in the apple peel. The melatonin content in 'Fuji' apple juice is comparable to the level of its flesh. Melatonin was consumed during the process of juicing due to its interaction with the oxidants. Melatonin addition significantly reduced the juice color change to brown (browning). The mechanism is that melatonin scavenges the free radicals, which was indicated by the ASBT analysis; therefore, inhibiting the conversion of o -diphenolic compounds into quinones. Most importantly, melatonin exhibited powerful anti-microorganism activity in juice. The exact mechanisms of this action are currently unknown. These effects of melatonin can preserve the quality and prolong the shelf life of apple juice. The results provide valuable information regarding commerciall apple juice processing and storage.

Ice Chemistry in Interstellar Dense Molecular Clouds, Protostellar Disks, and Comets

NASA Technical Reports Server (NTRS)

Sandford, Scott A.

2015-01-01

Despite the low temperatures (T less than 20K), low pressures, and low molecular densities found in much of the cosmos, considerable chemistry is expected to occur in many astronomical environments. Much of this chemistry happens in icy grain mantles on dust grains and is driven by ionizing radiation. This ionizing radiation breaks chemical bonds of molecules in the ices and creates a host of ions and radicals that can react at the ambient temperature or when the parent ice is subsequently warmed. Experiments that similar these conditions have demonstrated a rich chemistry associated with these environments that leads to a wide variety of organic products. Many of these products are of considerable interest to astrobiology. For example, the irradiation of simple ices has been shown to abiotically produce amino acids, nucleobases, quinones, and amphiphiles, all compounds that play key roles in modern biochemistry. This suggests extraterrestrial chemistry could have played a role in the origin of life on Earth and, by extension, do so on planets in other stellar systems.

Direct and indirect antioxidant activity of polyphenol- and isothiocyanate-enriched fractions from Moringa oleifera.

PubMed

Tumer, Tugba Boyunegmez; Rojas-Silva, Patricio; Poulev, Alexander; Raskin, Ilya; Waterman, Carrie

2015-02-11

Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate and 4-[(4'-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects.

Mechanistic insights into the bleaching of melanin by alkaline hydrogen peroxide.

PubMed

Smith, R A W; Garrett, B; Naqvi, K R; Fülöp, A; Godfrey, S P; Marsh, J M; Chechik, V

2017-07-01

This work aims to determine the roles of reactive oxygen species HO∙ and HO 2 - in the bleaching of melanins by alkaline hydrogen peroxide. Experiments using melanosomes isolated from human hair indicated that the HO∙ radical generated in the outside solution does not contribute significantly to bleaching. However, studies using soluble Sepia melanin demonstrated that both HO 2 - and HO∙ will individually bleach melanin. Additionally, when both oxidants are present, bleaching is increased dramatically in both rate and extent. Careful experimental design enabled the separation of the roles and effects of these key reactive species, HO∙ and HO 2 - . Rationalisation of the results presented, and review of previous literature, allowed the postulation of a simplified general scheme whereby the strong oxidant HO∙ is able to pre-oxidise melanin units to o-quinones enabling more facile ring opening by the more nucleophilic HO 2 - . In this manner the efficiency of the roles of both species is maximised. Copyright © 2017 Elsevier Inc. All rights reserved.

The 1:1 co-crystal of 2-bromo-naphthalene-1,4-dione and 1,8-di-hydroxy-anthracene-9,10-dione: crystal structure and Hirshfeld surface analysis.

PubMed

Tonin, Marlon D L; Garden, Simon J; Jotani, Mukesh M; Wardell, Solange M S V; Wardell, James L; Tiekink, Edward R T

2017-05-01

The asymmetric unit of the title co-crystal, C 10 H 5 BrO 2 ·C 14 H 8 O 4 [systematic name: 2-bromo-1,4-di-hydro-naphthalene-1,4-dione-1,8-dihy-droxy-9,10-di-hydro-anthracene-9,10-dione (1/1)], features one mol-ecule of each coformer. The 2-bromo-naphtho-quinone mol-ecule is almost planar [r.m.s deviation of the 13 non-H atoms = 0.060 Å, with the maximum deviations of 0.093 (1) and 0.099 (1) Å being for the Br atom and a carbonyl-O atom, respectively]. The 1,8-di-hydroxy-anthra-quinone mol-ecule is planar (r.m.s. deviation for the 18 non-H atoms is 0.022 Å) and features two intra-molecular hy-droxy-O-H⋯O(carbon-yl) hydrogen bonds. Dimeric aggregates of 1,8-di-hydroxy-anthra-quinone mol-ecules assemble through weak inter-molecular hy-droxy-O-H⋯O(carbon-yl) hydrogen bonds. The mol-ecular packing comprises stacks of mol-ecules of 2-bromo-naphtho-quinone and dimeric assembles of 1,8-di-hydroxy-anthra-quinone with the shortest π-π contact within a stack of 3.5760 (9) Å occurring between the different rings of 2-bromo-naphtho-quinone mol-ecules. The analysis of the Hirshfeld surface reveals the importance of the inter-actions just indicated but, also the contribution of additional C-H⋯O contacts as well as C=O⋯π inter-actions to the mol-ecular packing.

Evaluation of photosynthetic electrons derivation by exogenous redox mediators.

PubMed

Longatte, Guillaume; Fu, Han-Yi; Buriez, Olivier; Labbé, Eric; Wollman, Francis-André; Amatore, Christian; Rappaport, Fabrice; Guille-Collignon, Manon; Lemaître, Frédéric

2015-10-01

Oxygenic photosynthesis is the complex process that occurs in plants or algae by which the energy from the sun is converted into an electrochemical potential that drives the assimilation of carbon dioxide and the synthesis of carbohydrates. Quinones belong to a family of species commonly found in key processes of the Living, like photosynthesis or respiration, in which they act as electron transporters. This makes this class of molecules a popular candidate for biofuel cell and bioenergy applications insofar as they can be used as cargo to ship electrons to an electrode immersed in the cellular suspension. Nevertheless, such electron carriers are mostly selected empirically. This is why we report on a method involving fluorescence measurements to estimate the ability of seven different quinones to accept photosynthetic electrons downstream of photosystem II, the first protein complex in the light-dependent reactions of oxygenic photosynthesis. To this aim we use a mutant of Chlamydomonas reinhardtii, a unicellular green alga, impaired in electron downstream of photosystem II and assess the ability of quinones to restore electron flow by fluorescence. In this work, we defined and extracted a "derivation parameter" D that indicates the derivation efficiency of the exogenous quinones investigated. D then allows electing 2,6-dichlorobenzoquinone, 2,5-dichlorobenzoquinone and p-phenylbenzoquinone as good candidates. More particularly, our investigations suggested that other key parameters like the partition of quinones between different cellular compartments and their propensity to saturate these various compartments should also be taken into account in the process of selecting exogenous quinones for the purpose of deriving photoelectrons from intact algae. Copyright © 2015 Elsevier B.V. All rights reserved.

Electron Transfer Between Electrically Conductive Minerals and Quinones

NASA Astrophysics Data System (ADS)

Taran, Olga

2017-07-01

Long-distance electron transfer in marine environments couples physically separated redox half-reactions, impacting biogeochemical cycles of iron, sulfur and carbon. Bacterial bio-electrochemical systems that facilitate electron transfer via conductive filaments or across man-made electrodes are well known, but the impact of abiotic currents across naturally occurring conductive and semiconducitve minerals is poorly understood. In this paper I use cyclic voltammetry to explore electron transfer between electrodes made of common iron minerals (magnetite, hematite, pyrite, pyrrhotite, mackinawite and greigite), and hydroquinones - a class of organic molecules found in carbon-rich sediments. Of all tested minerals, only pyrite and magnetite showed an increase in electric current in the presence of organic molecules, with pyrite showing excellent electrocatalytic performance. Pyrite electrodes performed better than commercially available glassy carbon electrodes and showed higher peak currents, lower overpotential values and a smaller separation between oxidation and reduction peaks for each tested quinone. Hydroquinone oxidation on pyrite surfaces was reversible, diffusion controlled, and stable over a large number of potential cycles. Given the ubiquity of both pyrite and quinones, abiotic electron transfer between minerals and organic molecules is likely widespread in Nature and may contribute to several different phenomena, including anaerobic respiration of a wide variety of microorganisms in temporally anoxic zones or in the proximity of hydrothermal vent chimneys, as well as quinone cycling and the propagation of anoxic zones in organic rich waters. Finally, interactions between pyrite and quinones make use of electrochemical gradients that have been suggested as an important source of energy for the origins of life on Earth. Ubiquinones and iron sulfide clusters are common redox cofactors found in electron transport chains across all domains of life and interactions between quinones and pyrite might have been an early analogue of this ubiquitous systems.

Electronic connection between the quinone and cytochrome C redox pools and its role in regulation of mitochondrial electron transport and redox signaling.

PubMed

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. Copyright © 2015 the American Physiological Society.

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

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipoquinones of some spore-forming rods, lactic-acid bacteria and actinomycetes.

PubMed

Hess, A; Holländer, R; Mannheim, W

1979-11-01

The respiratory quinones of 73 strains of Gram-positive bacteria including spore-forming rods, lactic-acid bacteria and actinomyctes were examined. Menaquinones with seven isoprenoid units (MK-7) were the main quinone type found in representatives of the genus Bacillus and in Sporolactobacillus inulinus. However, a strain of B. thuringiensis produced MK-8 in addition to MK-7, and strains of B. lentus and B. pantothenticus appeared to produce MK-9 and MK-8, respectively, with no MK-7. In the clostridia and lactic-acid bacteria, no quinones were found, except in Pediococcus cerevisiae NCTC 8066 and Lactobacillus casei subsp. rhamnosus ATCC 7469, which contained menaquinones, and Streptococcus faecalis NCTC 775 and HIM 478-1, which contained demethylmenaquinones, in relatively low concentrations. Menaquinones were also found in the actinomycetes (except Actinomyces odontolyticus and Bifidobacterium bifidum which did not produce any quinones) and in Protaminobacter alboflavus ATCC 8458, the so-called Actinobacillus actinoides ATCC 15900 and Noguchia granulosis NCTC 10559.

Tumor cell membrane-targeting pH-dependent electron donor-acceptor fluorescence systems with low background signals.

PubMed

Han, Liang; Liu, Mingming; Ye, Deyong; Zhang, Ning; Lim, Ed; Lu, Jing; Jiang, Chen

2014-03-01

Minimizing the background signal is crucial for developing tumor-imaging techniques with sufficient specificity and sensitivity. Here we use pH difference between healthy tissues and tumor and tumor targeting delivery to achieve this goal. We synthesize fluorophore-dopamine conjugate as pH-dependent electron donor-acceptor fluorescence system. Fluorophores are highly sensitive to electron-transfer processes, which can alter their optical properties. The intrinsic redox properties of dopamine are oxidation of hydroquinone to quinone at basic pH and reduction of quinone to hydroquinone at acidic pH. Quinone can accept electron then quench fluorescence. We design tumor cell membrane-targeting carrier for delivery. We demonstrate quenched fluorophore-quinone can be specially transferred to tumor extracellular environment and tumor-accumulated fluorophore can be activated by acidic pH. These tumor-targeting pH-dependent electron donor-acceptor fluorescence systems may offer new opportunity for developing tumor-imaging techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aziridinyl-substituted benzo-1,4-quinones: A preliminary investigation on the theoretical and experimental studies of their structure and spectroscopic properties

NASA Astrophysics Data System (ADS)

Šarlauskas, Jonas; Tamulienė, Jelena; Čėnas, Narimantas

2017-05-01

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.

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...

Enzymatic redox properties of novel nitrotriazole explosives implications for their toxicity.

PubMed

Sarlauskas, Jonas; Nemeikaite-Ceniene, Ausra; Anusevicius, Zilvinas; Miseviciene, Lina; Maroziene, Audrone; Markevicius, Arvydas; Cenas, Narimantas

2004-01-01

The toxicity of conventional nitroaromatic explosives like 2,4,6-trinitrotoluene (TNT) is caused by their enzymatic free radical formation with the subsequent oxidative stress, the formation of alkylating nitroso and/or hydroxylamino metabolites, and oxyhemoglobin oxidation into methemoglobin. In order to get an insight into the mechanisms of toxicity of the novel explosives NTO (5-nitro-1,2,4-triazol-3-one) and ANTA (5-nitro-1,2,4-triazol-3-amine), we examined their reactions with the single-electron transferring flavoenzymes NADPH: cytochrome P-450 reductase and ferredoxin:NADP+ reductase, two-electron transferring flavoenzymes mammalian NAD(P)H:quinone oxidoreductase (DT-diaphorase), and Enterobacter cloacae NAD(P)H:nitroreductase, and their reactions with oxyhemoglobin. The reactivity of NTO and ANTA in the above reactions was markedly lower than that of TNT. The toxicity of NTO and ANTA in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was partly prevented by desferrioxamine and the antioxidant N,N'-diphenyl-p-phenylene diamine, and potentiated by 1,3-bis-(2-chloroethyl)-1-nitrosourea. This points to the involvement of oxidative stress in their cytotoxicity, presumably to the redox cycling of free radicals. The FLK cell line cytotoxicity and the methemoglobin formation in isolated human erythrocytes of NTO and ANTA were also markedly lower than those of TNT, and similar to those of nitrobenzene. Taken together, our data demonstrate that the low toxicity of nitrotriazole explosives may be attributed to their low electron-accepting properties.

Inhibition of in vitro leukotriene B4 biosynthesis in human neutrophil granulocytes and docking studies of natural quinones.

PubMed

Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Malik, Jan; Kokoska, Ladislav; Widowitz, Ute; Pribylova, Marie; Dvorakova, Marcela; Marsik, Petr; Schuster, Daniela; Bauer, Rudolf; Vanek, Tomas

2013-01-01

Quinones are compounds frequently contained in medicinal plants used for the treatment of inflammatory diseases. Therefore, the impact of plant-derived quinones on the arachidonic acid metabolic pathway is worthy of investigation. In this study, twenty-three quinone compounds of plant origin were tested in vitro for their potential to inhibit leukotriene B4 (LTB4) biosynthesis in activated human neutrophil granulocytes with 5-lipoxygenase (5-LOX) activity. The benzoquinones primin (3) and thymohydroquinone (4) (IC50 = 4.0 and 4.1 microM, respectively) showed activity comparable with the reference inhibitor zileuton (1C50 = 4.1 microM). Moderate activity was observed for the benzoquinone thymoquinone (2) (1C50 = 18.2 microM) and the naphthoquinone shikonin (1) (IC50 = 24.3 microM). The anthraquinone emodin and the naphthoquinone plumbagin (5) displayed only weak activities (IC50 > 50 microM). The binding modes of the active compounds were further evaluated in silico by molecular docking to the human 5-LOX crystal structure. This process supports the biological data and suggested that, although the redox potential is responsible for the quinone's activity on multiple targets, in the case of 5-LOX the molecular structure plays a vital role in the inhibition. The obtained results suggest primin as a promising compound for the development of dual COX-2/5-LOX inhibitors.

Enzyme-Initiated Quinone-Chitosan Conjugation Chemistry: Toward A General in Situ Strategy for High-Throughput Photoelectrochemical Enzymatic Bioanalysis.

PubMed

Wang, Guang-Li; Yuan, Fang; Gu, Tiantian; Dong, Yuming; Wang, Qian; Zhao, Wei-Wei

2018-02-06

Herein we report a general and novel strategy for high-throughput photoelectrochemical (PEC) enzymatic bioanalysis on the basis of enzyme-initiated quinone-chitosan conjugation chemistry (QCCC). Specifically, the strategy was illustrated by using a model quinones-generating oxidase of tyrosinase (Tyr) to catalytically produce 1,2-bezoquinone or its derivative, which can easily and selectively be conjugated onto the surface of the chitosan deposited PbS/NiO/FTO photocathode via the QCCC. Upon illumination, the covalently attached quinones could act as electron acceptors of PbS quantum dots (QDs), improving the photocurrent generation and thus allowing the elegant probing of Tyr activity. Enzyme cascades, such as alkaline phosphatase (ALP)/Tyr and β-galactosidase (Gal)/Tyr, were further introduced into the system for the successful probing of the corresponding targets. This work features not only the first use of QCCC in PEC bioanalysis but also the separation of enzymatic reaction from the photoelectrode as well as the direct signal recording in a split-type protocol, which enables quite convenient and high-throughput detection as compared to previous formats. More importantly, by using numerous other oxidoreductases that involve quinones as reactants/products, this protocol could serve as a common basis for the development of a new class of QCCC-based PEC enzymatic bioanalysis and further extended for general enzyme-labeled PEC bioanalysis of versatile targets.

Studies on the enzymes involved in puparial cuticle sclerotization in Drosophila melanogaster.

PubMed

Sugumaran, M; Giglio, L; Kundzicz, H; Saul, S; Semensi, V

1992-01-01

The properties of cuticular enzymes involved in sclerotization of Drosophila melanogaster puparium were examined. The cuticle-bound phenoloxidase from the white puparium exhibited a pH optimum of 6.5 in phosphate buffer and oxidized a variety of catecholic substrates such as 4-methylcatechol, N-beta-alanyldopamine, dopa, dopamine, N-acetyldopamine, catechol, norepinephrine, 3,4-dihydroxyphenylglycol, 3,4-dihydroxybenzoic acid, and 3,4-dihydroxyphenylacetic acid. Phenoloxidase inhibitors such as potassium cyanide and sodium fluoride inhibited the enzyme activity drastically, but phenylthiourea showed marginal inhibition only. This result, coupled with the fact that syringaldazine served as the substrate for the insoluble enzyme, confirmed that cuticular phenoloxidase is of the "laccase" type. In addition, we also examined the mode of synthesis of the sclerotizing precursor, 1,2-dehydro-N-acetyldopamine. Our results indicate that this catecholamine derivative is biosynthesized from N-acetyldopamine through the intermediate formation of N-acetyldopamine quinone and N-acetyldopamine quinone methide as established for Sarcophaga bullata [Saul, S. and Sugumaran, M., F.E.B.S. Letters 251, 69-73 (1989)]. Accordingly, successful solubilization and fractionation of cuticular enzymes involved in the introduction of a double bond in the side chain of N-acetyldopamine indicated that they included o-diphenoloxidase, 4-alkyl-o-quinone:p-quinone methide isomerase, and N-acetyldopamine quinone methide:dehydro N-acetyldopamine isomerase and not any side chain desaturase.

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 ...

Evidence for the formation of a quinone methide during the oxidation of the insect cuticular sclerotizing precursor 1,2-dehydro-N-acetyldopamine.

PubMed

Sugumaran, M; Semensi, V; Kalyanaraman, B; Bruce, J M; Land, E J

1992-05-25

1,2-Dehydro-N-acetyldopamine (dehydro-NADA) is an important catecholamine derivative involved in the cross-linking of insect cuticular components during sclerotization. Since sclerotization is a vital process for the survival of insects, and is closely related to melanogenesis, it is of interest to unravel the chemical mechanisms participating in this process. The present paper reports on the mechanism by which dehydro-NADA is oxidatively activated to form reactive intermediate(s) as revealed by pulse radiolysis, electron spin resonance spectroscopy, high performance liquid chromatography, and ultraviolet-visible spectroscopic analysis. Pulse radiolytic one-electron oxidation of dehydro-NADA by N3. (k = 5.3 x 10(9) M-1 s-1) or Br2.- (k = 7.5 x 10(8) M-1 s-1) at pH6 resulted in the rapid generation of the corresponding semiquinone radical, lambda max 400 nm, epsilon = 20,700 M-1 cm-1. This semiquinone decayed to form a second transient intermediate, lambda max 485 nm, epsilon = 8000 M-1 cm-1, via a second order disproportionation process, k = 6.2 x 10(8) M-1 s-1. At pH 6 in the presence of azide, the first order decay of this second intermediate occurred over milliseconds; the rate decreases at higher pH. At pH 6 in the presence of bromide, the intermediate decayed much more slowly over seconds, k = 0.15 s-1. Under such conditions, the dependence of the first order decay constant upon parent dehydro-NADA concentration led to a second order rate constant of 8.5 x 10(2) M-1 s-1 for reaction of the intermediate with the parent, probably to form benzodioxan "dimers." (The term dimer is used for convenience; the products are strictly bisdehydrodimers of dehydro-NADA (see "Discussion" and Fig. 11)) Rate constants of 5.9 x 10(5), 4.5 x 10(5), 2.8 x 10(4) and 3.5 x 10(4) M-1 s-1 were also obtained for decay of the second intermediate in the presence of cysteine, cysteamine, o-phenylenediamine, and p-aminophenol, respectively. By comparison with the UV-visible spectroscopic properties of the two-electron oxidized species derived from dehydro-NADA and from 1,2-dehydro-N-acetyldopa methyl ester, it is concluded that the transient intermediate exhibiting absorbance at 485 nm is the quinone methide tautomer of the o-quinone of dehydro-NADA. Sclerotization of insect cuticle is discussed in the light of these findings.

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.

FT–Raman investigation of bleaching of spruce thermomechanical pulp

Treesearch

U.P. Agarwal; L.L. Landucci

2004-01-01

Spruce thermomechanical pulp was bleached initially by alkaline hydrogen peroxide and then by sodium dithionite and sodium borohydride. Near-infrared Fourier-transform–Raman spectroscopy revealed that spectral differences were due primarily to coniferaldehyde and p-quinone structures in lignin, new direct evidence that bleaching removes p-quinone structures. In...

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

Engineering alfalfa to accumulate useful caffeic acid derivatives and characterization of hydroxycinnamoyl-CoA transferases from legumes

USDA-ARS?s Scientific Manuscript database

Some forages crops, such as red clover, accumulate high levels of caffeic acid derivatives. Oxidation of these o-diphenols to quinones by endogenous polyphenol oxidases (PPOs) and the subsequent reactions of these quinones (probably with endogenous plant proteases) result in a significant reduction ...

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...

Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones.

PubMed

Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Vuorinen, Anna; Malik, Jan; Dvorakova, Marcela; Marsik, Petr; Kokoska, Ladislav; Pribylova, Marie; Schuster, Daniela; Vanek, Tomas

2012-03-01

In this study, ten anthra-, nine naphtho-, and five benzoquinone compounds of natural origin and five synthetic naphthoquinones were assessed, using an enzymatic in vitro assay, for their potential to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2), the key enzymes of the arachidonic acid cascade. IC₅₀ values comparable with COX reference inhibitor indomethacin were recorded for several quinones (primin, alkannin, diospyrin, juglone, 7-methyljuglone, and shikonin). For some of the compounds, we suggest the redox potential of quinones as the mechanism responsible for in vitro COX inhibition because of the quantitative correlation with their pro-oxidant effect. Structure-relationship activity studies revealed that the substitutions at positions 2 and 5 play the key roles in the COX inhibitory and pro-oxidant actions of naphthoquinones. In contrast, the redox mechanism alone could not explain the activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional nonsteroidal anti-inflammatory drugs (NSAIDs). © Georg Thieme Verlag KG Stuttgart · New York.

Identification of Carotenoids and Isoprenoid Quinones from Asaia lannensis and Asaia bogorensis.

PubMed

Antolak, Hubert; Oracz, Joanna; Otlewska, Anna; Żyżelewicz, Dorota; Kręgiel, Dorota

2017-09-25

The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia , that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a laboratory liquid culture minimal medium with 2% sucrose. Carotenoids and isoprenoid quinones were investigated using UHPLC-DAD-ESI-MS analysis. In general, tested strains of Asaia spp. were able to produce 10 carotenoids and 3 isoprenoid quinones: menaquinone-7, menaquinone-8, and ubiquinone-10. The main identified carotenoids in Asaia lannensis strains were phytofluene, neurosporene, α-carotene, while for Asaia bogorensis , neurosporene, canthaxanthin, and zeaxanthin were noted. What is more, tested Asaia spp. were able to produce myxoxanthophyll, which has so far been identified primarily in cyanobacteria. The results show that A. lannensis are characterized by statistically higher concentrations of produced carotenoids, as well as a greater variety of these compounds. We have noted that carotenoids were not only accumulated by bacterial cells, but also some strains of A. lannensis produced extracellular carotenoids.

Crystal structures of 1-hy­droxy-4-prop­yloxy-9,10-anthra­quinone and its acetyl derivative

PubMed Central

Nakagawa, Hidemi; Kitamura, Chitoshi

2017-01-01

1-Hy­droxy-4-prop­yloxy-9,10-anthra­quinone, C17H14O4, (I), and its acetyl derivative, 4-acet­yloxy-4-prop­yloxy-9,10-anthra­quinone, C19H16O5, (II), were synthesized from the commercially available dye quinizarin. In both compounds, the anthra­quinone frameworks are close to planarity. There is a large difference in the conformation of the prop­yloxy group; the mol­ecule of (I) adopts a gauche conformation [O—C—C—C = −64.4 (2)°], although the mol­ecule of (II) takes a trans-planar conformation (zigzag) [O—C—C—C = 176.1 (3)°]. In the mol­ecule of (I), there is an intra­molecular O—H⋯O hydrogen bond. In both crystals, the mol­ecules are linked by C—H ⋯O hydrogen bonds. A difference in the mol­ecular arrangements of (I) and (II) is found along the stacking directions. PMID:29250400

Detection of Free and Protein-Bound ortho-Quinones by Near-Infrared Fluorescence.

PubMed

Mazzulli, Joseph R; Burbulla, Lena F; Krainc, Dimitri; Ischiropoulos, Harry

2016-02-16

Aging and oxidative stress are two prominent pathological mechanisms for Parkinson's disease (PD) that are strongly associated with the degeneration of dopamine (DA) neurons in the midbrain. DA and other catechols readily oxidize into highly reactive o-quinone species that are precursors of neuromelanin (NM) pigment and under pathological conditions can modify and damage macromolecules. The role of DA oxidation in PD pathogenesis remains unclear in part due to the lack of appropriate disease models and the absence of a simple method for the quantification of DA-derived oxidants. Here, we describe a rapid, simple, and reproducible method for the quantification of o-quinones in cells and tissues that relies on the near-infrared fluorescent properties of these species. Importantly, we demonstrate that catechol-derived oxidants can be quantified in human neuroblastoma cells and midbrain dopamine neurons derived from induced pluripotent stem cells, providing a novel model to study the downstream actions of o-quinones. This method should facilitate further study of oxidative stress and DA oxidation in PD and related diseases that affect the dopaminergic system.

Strecker Aldehyde Formation in Wine: New Insights into the Role of Gallic Acid, Glucose, and Metals in Phenylacetaldehyde Formation.

PubMed

Monforte, Ana Rita; Martins, Sara I F S; Silva Ferreira, Antonio C

2018-03-14

Strecker degradation (SD) leading to the formation of phenylacetaldehyde (PA) was studied in wine systems. New insights were gained by using two full factorial designs focusing on the effects of (1) pH and (2) temperature. In each design of experiments (DoE) three factors, glucose, gallic acid, and metals at two levels (present or absence), were varied while phenylalanine was kept constant. The obtained results gave a clear indication, with statistical significance, that in wine conditions, the SD occurs in the presence of metals preferentially via the phenolic oxidation independent of the temperature (40 or 80 °C). The reaction of the amino acid with the o-quinone formed by the oxidation of the gallic acid seems to be favored when compared with the SD promoted by the reaction with α-dicarbonyls formed by MR between glucose and phenylalanine. In fact, kinetics results showed that the presence of glucose had an inhibitory effect on PA rate of formation. PA formation was 4 times higher in the control wine when compared to the same wine with 10 g/L glucose added. By gallic acid quinone quantitation it is shown that glucose affects directly the concentration of the quinone. decreasing the rate of quinone formation. This highlights the role of sugar in o-quinone concentration and consequently in the impact on Strecker aldehyde formation, a promising new perspective regarding wine shelf-life understanding.

Combined molecular modelling and 3D-QSAR study for understanding the inhibition of NQO1 by heterocyclic quinone derivatives.

PubMed

López-Lira, Claudia; Alzate-Morales, Jans H; Paulino, Margot; Mella-Raipán, Jaime; Salas, Cristian O; Tapia, Ricardo A; Soto-Delgado, Jorge

2018-01-01

A combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular modelling methods were used to understand the potent inhibitory NAD(P)H:quinone oxidoreductase 1 (NQO1) activity of a set of 52 heterocyclic quinones. Molecular docking results indicated that some favourable interactions of key amino acid residues at the binding site of NQO1 with these quinones would be responsible for an improvement of the NQO1 activity of these compounds. The main interactions involved are hydrogen bond of the amino group of residue Tyr128, π-stacking interactions with Phe106 and Phe178, and electrostatic interactions with flavin adenine dinucleotide (FADH) cofactor. Three models were prepared by 3D-QSAR analysis. The models derived from Model I and Model III, shown leave-one-out cross-validation correlation coefficients (q 2 LOO ) of .75 and .73 as well as conventional correlation coefficients (R 2 ) of .93 and .95, respectively. In addition, the external predictive abilities of these models were evaluated using a test set, producing the predicted correlation coefficients (r 2 pred ) of .76 and .74, respectively. The good concordance between the docking results and 3D-QSAR contour maps provides helpful information about a rational modification of new molecules based in quinone scaffold, in order to design more potent NQO1 inhibitors, which would exhibit highly potent antitumor activity. © 2017 John Wiley & Sons A/S.

Electrochemical measurement of lateral diffusion coefficients of ubiquinones and plastoquinones of various isoprenoid chain lengths incorporated in model bilayers.

PubMed Central

Marchal, D; Boireau, W; Laval, J M; Moiroux, J; Bourdillon, C

1998-01-01

The long-range diffusion coefficients of isoprenoid quinones in a model of lipid bilayer were determined by a method avoiding fluorescent probe labeling of the molecules. The quinone electron carriers were incorporated in supported dimyristoylphosphatidylcholine layers at physiological molar fractions (<3 mol%). The elaborate bilayer template contained a built-in gold electrode at which the redox molecules solubilized in the bilayer were reduced or oxidized. The lateral diffusion coefficient of a natural quinone like UQ10 or PQ9 was 2.0 +/- 0.4 x 10(-8) cm2 s(-1) at 30 degrees C, two to three times smaller than the diffusion coefficient of a lipid analog in the same artificial bilayer. The lateral mobilities of the oxidized or reduced forms could be determined separately and were found to be identical in the 4-13 pH range. For a series of isoprenoid quinones, UQ2 or PQ2 to UQ10, the diffusion coefficient exhibited a marked dependence on the length of the isoprenoid chain. The data fit very well the quantitative behavior predicted by a continuum fluid model in which the isoprenoid chains are taken as rigid particles moving in the less viscous part of the bilayer and rubbing against the more viscous layers of lipid heads. The present study supports the concept of a homogeneous pool of quinone located in the less viscous region of the bilayer. PMID:9545054

Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae

PubMed Central

Castro, Frederico Augusto Vieira; Mariani, Diana; Panek, Anita Dolly; Eleutherio, Elis Cristina Araújo; Pereira, Marcos Dias

2008-01-01

Background Quinones are compounds extensively used in studies of oxidative stress due to their role in plants as chemicals for defense. These compounds are of great interest for pharmacologists and scientists, in general, because several cancer chemotherapeutic agents contain the quinone nucleus. However, due to differences in structures and diverse pharmacological effects, the exact toxicity mechanisms exerted by quinones are far from elucidatation. Methodology/Principal Findings Using Saccharomyces cerevisiae, we evaluated the main mechanisms of toxicity of two naphthoquinones, menadione and plumbagin, by determining tolerance and oxidative stress biomarkers such as GSH and GSSG, lipid peroxidation levels, as well as aconitase activity. The importance of glutathione transferases (GST) in quinone detoxification was also addressed. The GSSG/GSH ratio showed that menadione seemed to exert its toxicity mainly through the generation of ROS while plumbagin acted as an electrophile reacting with GSH. However, the results showed that, even by different pathways, both drugs were capable of generating oxidative stress through their toxic effects. Our results showed that the control strain, BY4741, and the glutathione transferase deficient strains (gtt1Δ and gtt2Δ) were sensitive to both compounds. With respect to the role of GST isoforms in cellular protection against quinone toxicity, we observed that the Gtt2 deficient strain was unable to overcome lipid peroxidation, even after a plumbagin pre-treatment, indicating that this treatment did not improve tolerance when compared with the wild type strain. Cross-tolerance experiments confirmed distinct cytotoxicity mechanisms for these naphthoquinones since only a pre-treatment with menadione was able to induce acquisition of tolerance against stress with plumbagin. Conclusions/Significance These results suggest different responses to menadione and plumbagin which could be due to the fact that these compounds use different mechanisms to exert their toxicity. In addition, the Gtt2 isoform seemed to act as a general protective factor involved in quinone detoxification. PMID:19098979

Increased Isoprenoid Quinone Concentration Modulates Membrane Fluidity in Listeria monocytogenes at Low Growth Temperatures.

PubMed

Seel, Waldemar; Flegler, Alexander; Zunabovic-Pichler, Marija; Lipski, André

2018-07-01

Listeria monocytogenes is a food pathogen capable of growing at a broad temperature range from 50°C to refrigerator temperatures. A key requirement for bacterial activity and growth at low temperatures is the ability to adjust the membrane lipid composition to maintain cytoplasmic membrane fluidity. In this study, we confirmed earlier findings that the extents of fatty acid profile adaptation differed between L. monocytogenes strains. We were able to demonstrate for isolates from food that growth rates at low temperatures and resistance to freeze-thaw stress were not impaired by a lower adaptive response of the fatty acid composition. This indicated the presence of a second adaptation mechanism besides temperature-regulated fatty acid synthesis. For strains that showed weaker adaptive responses in their fatty acid profiles to low growth temperature, we could demonstrate a significantly higher concentration of isoprenoid quinones. Three strains even showed a higher quinone concentration after growth at 6°C than at 37°C, which is contradictory to the reduced respiratory activity at lower growth temperatures. Analyses of the membrane fluidity in vivo by measuring generalized polarization and anisotropy revealed modulation of the transition phase. Strains with increased quinone concentrations showed an expanded membrane transition phase in contrast to strains with pronounced adaptations of fatty acid profiles. The correlation between quinone concentration and membrane transition phase expansion was confirmed by suppression of quinone synthesis. A reduced quinone concentration resulted in a narrower transition phase. Expansion of the phase transition zone by increasing the concentration of non-fatty acid membrane lipids is discussed as an additional mechanism improving adaptation to temperature shifts for L. monocytogenes strains. IMPORTANCE Listeria monocytogenes is a foodborne pathogen with an outstanding temperature range for growth. The ability for growth at temperatures close to the freezing point constitutes a serious contamination potential for cold stored food. The only known mechanism of the species for adaptation of membrane fluidity is modification of the membrane fatty acid composition. We were able to demonstrate that, at least for some strains, this adaptation mechanism is supported by regulation of the menaquinone concentration. The increase of this neutral membrane lipid is correlated with fluidization of the membrane under low-temperature conditions and therefore represents a fatty acid-independent mechanism for adaptation to low temperatures. Copyright © 2018 American Society for Microbiology.

Quinones from Heliotropium ovalifolium.

PubMed

Guntern, A; Ioset, J R; Queiroz, E F; Foggin, C M; Hostettmann, K

2001-10-01

Two new benzoquinones, heliotropinones A and B, have been isolated from the aerial parts of Heliotropium ovalifolium. Their structures were elucidated by spectrometric methods including high resolution electrospray ionization (ESI-HR), EI mass spectrometry, 1H, 13C and 2D NMR experiments. The two quinones demonstrated antifungal activities against Cladosporium cucumerinum and Candida albicans as well as antibacterial activity against Bacillus subtilis.

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...

Quinones from plants of northeastern Brazil: structural diversity, chemical transformations, NMR data and biological activities.

PubMed

Lemos, Telma L G; Monte, Francisco J Q; Santos, Allana Kellen L; Fonseca, Aluisio M; Santos, Hélcio S; Oliveira, Mailcar F; Costa, Sonia M O; Pessoa, Otilia D L; Braz-Filho, Raimundo

2007-05-20

The present review focus in quinones found in species of Brazilian northeastern Capraria biflora, Lippia sidoides, Lippia microphylla and Tabebuia serratifolia. The review cover ethnopharmacological aspects including photography of species, chemical structure feature, NMR datea and biological properties. Chemical transformations of lapachol to form enamine derivatives and biological activities are discussed.

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...

Biomimetic Modeling of Copper Complexes: A Study of Enantioselective Catalytic Oxidation on D-(+)-Catechin and L-( − )-Epicatechin with Copper Complexes

PubMed Central

Mutti, Francesco G.; Pievo, Roberta; Sgobba, Maila; Gullotti, Michele; Santagostini, Laura

2008-01-01

The biomimetic catalytic oxidations of the dinuclear and trinuclear copper(II) complexes versus two catechols, namely, D-(+)-catechin and L-( − )-epicatechin to give the corresponding quinones are reported. The unstable quinones were trapped by the nucleophilic reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH), and have been calculated the molar absorptivities of the different quinones. The catalytic efficiency is moderate, as inferred by kinetic constants, but the complexes exhibit significant enantio-differentiating ability towards the catechols, albeit for the dinuclear complexes, this enantio-differentiating ability is lower. In all cases, the preferred enantiomeric substrate is D-(+)-catechin to respect the other catechol, because of the spatial disposition of this substrate. PMID:18825268

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

Deodorizing Substance in Black Cumin (Nigella sativa L.) Seed Oil.

PubMed

Nakasugi, Toru; Murakawa, Takushi; Shibuya, Koji; Morimoto, Masanori

2017-08-01

A deodorizing substance in black cumin (Nigella sativa L.), a spice for curry and vegetable foods in Southwest Asia, was examined. The essential oil prepared from the seeds of this plant exhibited strong deodorizing activity against methyl mercaptan, which is a main factor in oral malodor. After purification with silica gel column chromatography, the active substance in black cumin seed oil was identified as thymoquinone. This monoterpenic quinone functions as the main deodorizing substance in this oil against methyl mercaptan. Metabolite analysis suggested that the deodorizing activity may be generated by the addition of a reactive quinone molecule to methyl mercaptan. In the present study, the menthane-type quinone and phenol derivatives exhibited deodorizing activities via this mechanism.

Cancer chemopreventive and anticancer evaluation of extracts and fractions from marine macro- and microorganisms collected from Twilight Zone waters around Guam.

PubMed

Schupp, Peter J; Kohlert-Schupp, Claudia; Whitefield, Susanna; Engemann, Anna; Rohde, Sven; Hemscheidt, Thomas; Pezzuto, John M; Kondratyuk, Tamara P; Park, Eun-Jung; Marler, Laura; Rostama, Bahman; Wright, Anthony D

2009-12-01

The cancer chemopreventive and cytotoxic properties of 50 extracts derived from Twilight Zone (50-150 m) sponges, gorgonians and associated bacteria, together with 15 extracts from shallow water hard corals, as well as 16 fractions derived from the methanol solubles of the Twilight Zone sponge Suberea sp, were assessed in a series of bioassays. These assays included: Induction of quinone reductase (QR), inhibition of TNF-alpha activated nuclear factor kappa B (NFkappaB), inhibition of aromatase, interaction with retinoid X receptor (RXR), inhibition of nitric oxide (NO) synthase, inhibition 2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), and inhibition of HL-60 and MCF-7 cell proliferation. The results of these assays showed that at least 10 extracts and five fractions inhibited NFkappaB by greater than 60%, two extracts and two fractions inhibited DPPH by more than 50%, nine extracts and two fractions affected the survival of HL-60 cells, no extracts or fractions affected RXR, three extracts and six fractions affected quinone reductase (QR), three extracts and 12 fractions significantly inhibited aromatase, four extracts and five fractions inhibited nitric oxide synthase, and one extract and no fractions inhibited the growth of MCF-7 cells by more than 95%. These data revealed the tested samples to have many and varied activities, making them, as shown with the extract of the Suberea species, useful starting points for further fractionation and purification. Moreover, the large number of samples demonstrating activity in only one or sometimes two assays accentuates the potential of the Twilight Zone, as a largely unexplored habitat, for the discovery of selectively bioactive compounds. The overall high hit rate in many of the employed assays is considered to be a significant finding in terms of "normal" hit rates associated with similar samples from shallower depths.

The measured and calculated affinity of methyl and methoxy substituted benzoquinones for the QA site of bacterial reaction centers

PubMed Central

Zheng, Zhong; Dutton, P. Leslie; Gunner, M. R.

2010-01-01

Quinones play important roles in mitochondrial and photosynthetic energy conversion acting as intramembrane, mobile electron and proton carriers between catalytic sites in various electron transfer proteins. They display different affinity, selectivity, functionality and exchange dynamics in different binding sites. The computational analysis of quinone binding sheds light on the requirements for quinone affinity and specificity. The affinities of ten oxidized, neutral benzoquinones (BQs) were measured for the high affinity QA site in the detergent solubilized Rhodobacter sphaeroides bacterial photosynthetic reaction center. Multi-Conformation Continuum Electrostatics (MCCE) was then used to calculate their relative binding free energies by Grand Canonical Monte Carlo sampling with a rigid protein backbone, flexible ligand and side chain positions and protonation states. Van der Waals and torsion energies, Poisson-Boltzmann continuum electrostatics and accessible surface area dependent ligand-solvent interactions are considered. An initial, single cycle of GROMACS backbone optimization improves the match with experiment as do coupled ligand and side chain motions. The calculations match experiment with an RMSD of 2.29 and a slope of 1.28. The affinities are dominated by favorable protein-ligand van der Waals rather than electrostatic interactions. Each quinone appears in a closely clustered set of positions. Methyl and methoxy groups move into the same positions as found for the native quinone. Difficulties putting methyls into methoxy sites are observed. Calculations using an SAS dependent implicit van der Waals interaction smoothed out small clashes, providing a better match to experiment with a RMSD of 0.77 and a slope of 0.97. PMID:20607696

Modeling electron transfer in photosystem I.

PubMed

Makita, Hiroki; Hastings, Gary

2016-06-01

Nanosecond to millisecond time-resolved absorption spectroscopy has been used to study electron transfer processes in photosystem I particles from Synechocystis sp. PCC 6803 with eight different quinones incorporated into the A1 binding site, at both 298 and 77K. A detailed kinetic model was constructed and solved within the context of Marcus electron transfer theory, and it was found that all of the data could be well described only if the in situ midpoint potentials of the quinones fell in a tightly defined range. For photosystem I with phylloquinone incorporated into the A1 binding site all of the time-resolved optical data is best modeled when the in situ midpoint potential of phylloquinone on the A/B branch is -635/-690 mV, respectively. With the midpoint potential of the F(X) iron sulfur cluster set at -680 mV, this indicates that forward electron transfer from A(1)(-) to F(X) is slightly endergonic/exergonic on the A/B branch, respectively. Additionally, for forward electron transfer from A(1)(-) to F(X), on both the A and B branches the reorganization energy is close to 0.7 eV. Reorganization energies of 0.4 or 1.0 eV are not possible. For the eight different quinones incorporated, the same kinetic model was used, allowing us to establish in situ redox potentials for all of the incorporated quinones on both branches. A linear correlation was found between the in situ and in vitro midpoint potentials of the quinones on both branches. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Electron transfer of quinone self-assembled monolayers on a gold electrode.

PubMed

Nagata, Morio; Kondo, Masaharu; Suemori, Yoshiharu; Ochiai, Tsuyoshi; Dewa, Takehisa; Ohtsuka, Toshiaki; Nango, Mamoru

2008-06-15

Dialkyl disulfide-linked naphthoquinone, (NQ-Cn-S)2, and anthraquinone, (AQ-Cn-S)2, derivatives with different spacer alkyl chains (Cn: n=2, 6, 12) were synthesized and these quinone derivatives were self-assembled on a gold electrode. The formation of self-assembled monolayers (SAMs) of these derivatives on a gold electrode was confirmed by infrared reflection-absorption spectroscopy (IR-RAS). Electron transfer between the derivatives and the gold electrode was studied by cyclic voltammetry. On the cyclic voltammogram a reversible redox reaction between quinone (Q) and hydroquinone (QH2) was clearly observed under an aqueous condition. The formal potentials for NQ and AQ derivatives were -0.48 and -0.58 V, respectively, that did not depend on the spacer length. The oxidation and reduction peak currents were strongly dependent on the spacer alkyl chain length. The redox behavior of quinone derivatives depended on the pH condition of the buffer solution. The pH dependence was in agreement with a theoretical value of E 1/2 (mV)=E'-59pH for 2H+/2e(-) process in the pH range 3-11. In the range higher than pH 11, the value was estimated with E 1/2 (mV)=E'-30pH , which may correspond to H+/2e(-) process. The tunneling barrier coefficients (beta) for NQ and AQ SAMs were determined to be 0.12 and 0.73 per methylene group (CH2), respectively. Comparison of the structures and the alkyl chain length of quinones derivatives on these electron transfers on the electrode is made.

The protective effect of Nigella sativa against liver injury: a review.

PubMed

Mollazadeh, Hamid; Hosseinzadeh, Hossein

2014-12-01

Nigella sativa (Family Ranunculaceae) is a widely used medicinal plant throughout the world. N. sativa is referred in the Middle East as a part of an overall holistic approach to health. Pharmacological properties of N. sativa including immune stimulant, hypotensive, anti-inflammatory, anti-cancer, antioxidant, hypoglycemic, spasmolytic and bronchodilator have been shown. Reactive oxygen species (ROS) and oxidative stress are known as the major causes of many diseases such as liver injury and many substances and drugs can induce oxidative damage by generation of ROS in the body. Many pharmacological properties of N. sativa are known to be attributed to the presence of thymoquinone and its antioxidant effects. Thymoquinone protects liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and glutathione level, radical scavengering, increasing the activity of quinone reductase, catalase, superoxide dismutase and glutathione transferase, inhibition of NF-κB activity and inhibition of both cyclooxygenase and lipoxygenase. Therefore, this review aimed to highlight the roles of ROS in liver diseases and the mechanisms of N. sativa in prevention of liver injury.

Direct and Indirect Antioxidant Activity of Polyphenol- and Isothiocyanate-Enriched Fractions from Moringa oleifera

PubMed Central

Boyunegmez Tumer, Tugba; Rojas-Silva, Patricio; Poulev, Alexander; Raskin, Ilya; Waterman, Carrie

2016-01-01

Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]-isothiocyanate and 4-[(4′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects. PMID:25605589

CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

EPA Science Inventory

Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

Widespread ability of fungi to drive quinone redox cycling for biodegradation.

PubMed

Krueger, Martin C; Bergmann, Michael; Schlosser, Dietmar

2016-06-01

Wood-rotting fungi possess remarkably diverse extracellular oxidation mechanisms, including enzymes, such as laccase and peroxidases, and Fenton chemistry. The ability to biologically drive Fenton chemistry by the redox cycling of quinones has previously been reported to be present in both ecologically diverging main groups of wood-rotting basidiomycetes. Therefore, we investigated whether it is even more widespread among fungal organisms. Screening of a diverse selection of a total of 18 ascomycetes and basidiomycetes for reduction of the model compound 2,6-dimethoxy benzoquinone revealed that all investigated strains were capable of reducing it to its corresponding hydroquinone. In a second step, depolymerization of the synthetic polymer polystyrene sulfonate was used as a proxy for quinone-dependent Fenton-based biodegradation capabilities. A diverse subset of the strains, including environmentally ubiquitous molds, white-rot fungi, as well as peatland and aquatic isolates, caused substantial depolymerization indicative for the effective employment of quinone redox cycling as biodegradation tool. Our results may also open up new paths to utilize diverse fungi for the bioremediation of recalcitrant organic pollutants. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Photoproduction of hydrogen peroxide in aqueous solution from model compounds for chromophoric dissolved organic matter (CDOM).

PubMed

Clark, Catherine D; de Bruyn, Warren; Jones, Joshua G

2014-02-15

To explore whether quinone moieties are important in chromophoric dissolved organic matter (CDOM) photochemistry in natural waters, hydrogen peroxide (H2O2) production and associated optical property changes were measured in aqueous solutions irradiated with a Xenon lamp for CDOM model compounds (dihydroquinone, benzoquinone, anthraquinone, napthoquinone, ubiquinone, humic acid HA, fulvic acid FA). All compounds produced H2O2 with concentrations ranging from 15 to 500 μM. Production rates were higher for HA vs. FA (1.32 vs. 0.176 mM h(-1)); values ranged from 6.99 to 0.137 mM h(-1) for quinones. Apparent quantum yields (Θ app; measure of photochemical production efficiency) were higher for HA vs. FA (0.113 vs. 0.016) and ranged from 0.0018 to 0.083 for quinones. Dihydroquinone, the reduced form of benzoquinone, had a higher production rate and efficiency than its oxidized form. Post-irradiation, quinone compounds had absorption spectra similar to HA and FA and 3D-excitation-emission matrix fluorescence spectra (EEMs) with fluorescent peaks in regions associated with CDOM. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optical properties of humic substances and CDOM: effects of borohydride reduction.

PubMed

Ma, Jiahai; Del Vecchio, Rossana; Golanoski, Kelli S; Boyle, Erin S; Blough, Neil V

2010-07-15

Treatment of Suwanee River humic (SRHA) and fulvic (SRFA) acids, a commercial lignin (LAC), and a series of solid phase extracts (C18) from the Middle Atlantic Bight (MAB extracts) with sodium borohydride (NaBH(4)), a selective reductant of carbonyl-containing compounds including quinones and aromatic ketones, produces a preferential loss of visible absorption (> or = 50% for SRFA) and substantially enhanced, blue-shifted fluorescence emission (2- to 3-fold increase). Comparison of the results with those obtained from a series of model quinones and hydroquinones demonstrates that these spectral changes cannot be assigned directly to the absorption and emission of visible light by quinones/hydroquinones. Instead, these results are consistent with a charge transfer model in which the visible absorption is due primarily to charge transfer transitions arising among hydroxy- (methoxy-) aromatic donors and carbonyl-containing acceptors. Unlike most of the model hydroquinones, the changes in optical properties of the natural samples following NaBH(4) reduction were largely irreversible in the presence of air and following addition of a Cu(2+) catalyst, providing tentative evidence that aromatic ketones (or other similar carbonyl-containing structures) may play a more important role than quinones in the optical properties of these materials.

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

Catalyzed and Electrocatalyzed Oxidation of l-Tyrosine and l-Phenylalanine to Dopachrome by Nanozymes.

PubMed

Hou, Jianwen; Vázquez-González, Margarita; Fadeev, Michael; Liu, Xia; Lavi, Ronit; Willner, Itamar

2018-06-13

Catalyzed oxygen insertion into C-H bonds represents a continuous challenge in chemistry. Particularly, driving this process at ambient temperature and aqueous media represents a "holy grail" in catalysis. We report on the catalyzed cascade transformations of l-tyrosine or l-phenylalanine to dopachrome in the presence of l-ascorbic acid/H 2 O 2 as oxidizing mixture and CuFe-Prussian Blue-like nanoparticles, Fe 3 O 4 nanoparticles or Au nanoparticles as catalysts. The process involves the primary transformation of l-tyrosine to l-DOPA that is further oxidized to dopachrome. The transformation of l-phenylalanine to dopachrome in the presence of CuFe-Prussian Blue-like nanoparticles and l-ascorbic acid/H 2 O 2 involves in the first step the formation of l-tyrosine and, subsequently, the operation of the catalytic oxidation cascade of l-tyrosine to l-DOPA and dopachrome. Electron spin resonance experiments demonstrate that ascorbate radicals and hydroxyl radicals play cooperative functions in driving the different oxygen-insertion processes. In addition, the aerobic elecrocatalyzed oxidation of l-tyrosine to dopachrome in the presence of naphthoquinone-modified Fe 3 O 4 nanoparticles and l-ascorbic acid is demonstrated. In this system, magnetic-field attraction of the naphthoquinone-modified Fe 3 O 4 nanoparticles onto the electrode allows the quinone-mediated electrocatalyzed reduction of O 2 to H 2 O 2 (bias potential -0.5 V vs SCE). The electrogenerated H 2 O 2 is then utilized to promote the transformation of l-tyrosine to dopachrome in the presence of l-ascorbic acid and Fe 3 O 4 catalyst.

Iron-Mediated Oxidation of Methoxyhydroquinone under Dark Conditions: Kinetic and Mechanistic Insights.

PubMed

Yuan, Xiu; Davis, James A; Nico, Peter S

2016-02-16

Despite the biogeochemical significance of the interactions between natural organic matter (NOM) and iron species, considerable uncertainty still remains as to the exact processes contributing to the rates and extents of complexation and redox reactions between these important and complex environmental components. Investigations on the reactivity of low-molecular-weight quinones, which are believed to be key redox active compounds within NOM, toward iron species, could provide considerable insight into the kinetics and mechanisms of reactions involving NOM and iron. In this study, the oxidation of 2-methoxyhydroquinone (MH2Q) by ferric iron (Fe(III)) under dark conditions in the absence and presence of oxygen was investigated within a pH range of 4-6. Although Fe(III) was capable of stoichiometrically oxidizing MH2Q under anaerobic conditions, catalytic oxidation of MH2Q was observed in the presence of O2 due to further cycling between oxygen, semiquinone radicals, and iron species. A detailed kinetic model was developed to describe the predominant mechanisms, which indicated that both the undissociated and monodissociated anions of MH2Q were kinetically active species toward Fe(III) reduction, with the monodissociated anion being the key species accounting for the pH dependence of the oxidation. The generated radical intermediates, namely semiquinone and superoxide, are of great importance in reaction-chain propagation. The kinetic model may provide critical insight into the underlying mechanisms of the thermodynamic and kinetic characteristics of metal-organic interactions and assist in understanding and predicting the factors controlling iron and organic matter transformation and bioavailability in aquatic systems.

X-ray and EPR Characterization of the Auxiliary Fe-S Clusters in the Radical SAM Enzyme PqqE.

PubMed

Barr, Ian; Stich, Troy A; Gizzi, Anthony S; Grove, Tyler L; Bonanno, Jeffrey B; Latham, John A; Chung, Tyler; Wilmot, Carrie M; Britt, R David; Almo, Steven C; Klinman, Judith P

2018-02-27

The Radical SAM (RS) enzyme PqqE catalyzes the first step in the biosynthesis of the bacterial cofactor pyrroloquinoline quinone, forming a new carbon-carbon bond between two side chains within the ribosomally synthesized peptide substrate PqqA. In addition to the active site RS 4Fe-4S cluster, PqqE is predicted to have two auxiliary Fe-S clusters, like the other members of the SPASM domain family. Here we identify these sites and examine their structure using a combination of X-ray crystallography and Mössbauer and electron paramagnetic resonance (EPR) spectroscopies. X-ray crystallography allows us to identify the ligands to each of the two auxiliary clusters at the C-terminal region of the protein. The auxiliary cluster nearest the RS site (AuxI) is in the form of a 2Fe-2S cluster ligated by four cysteines, an Fe-S center not seen previously in other SPASM domain proteins; this assignment is further supported by Mössbauer and EPR spectroscopies. The second, more remote cluster (AuxII) is a 4Fe-4S center that is ligated by three cysteine residues and one aspartate residue. In addition, we examined the roles these ligands play in catalysis by the RS and AuxII clusters using site-directed mutagenesis coupled with EPR spectroscopy. Lastly, we discuss the possible functional consequences that these unique AuxI and AuxII clusters may have in catalysis for PqqE and how these may extend to additional RS enzymes catalyzing the post-translational modification of ribosomally encoded peptides.

Intramolecular Aza-Diels-Alder Reactions of ortho-Quinone Methide Imines: Rapid, Catalytic, and Enantioselective Assembly of Benzannulated Quinolizidines.

PubMed

Kretzschmar, Martin; Hofmann, Fabian; Moock, Daniel; Schneider, Christoph

2018-04-16

Aza-Diels-Alder reactions (ADARs) are powerful processes that furnish N-heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi- and polycyclic systems with high stereoselectivity. We report herein a novel Brønsted acid catalyzed process in which ortho-quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one-step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo- and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho-quinone methide imine formation, and ADAR. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wide-band, time-resolved photoacoustic study of electron-transfer reactions. Photoexcited magnesium porphyrin and quinones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feitelson, J.; Mauzerall, D.C.

1993-08-12

Wide-band, time-resolved, pulsed photoacoustics has been employed to study the electron-transfer reaction between a triplet magnesium porphyrin and various quinones in polar and nonpolar solvents. The reaction rate constants are near encounter limited. The yield of triplet state is 70% in both solvents. The yield of ions is 85% in the former and zero in the latter, in agreement with spin dephasing time and escape times from the Coulomb wells in the two solvents. In methanol the plot of measured heat output versus quinone redox potential is linear. This implies that the entropy of electron transfer is constant through themore » series, but it may not be negligible. 16 refs., 2 figs., 1 tab.« less

Site-directed mutagenesis of conserved cysteine residues in NqrD and NqrE subunits of Na+-translocating NADH:quinone oxidoreductase.

PubMed

Fadeeva, M S; Bertsova, Y V; Verkhovsky, M I; Bogachev, A V

2008-02-01

Each of two hydrophobic subunits of Na+-translocating NADH:quinone oxidoreductase (NQR), NqrD and NqrE, contain a pair of strictly conserved cysteine residues within their transmembrane alpha-helices. Site-directed mutagenesis showed that substitutions of these residues in NQR of Vibrio harveyi blocked the Na+-dependent and 2-n-heptyl-4-hydroxyquinoline N-oxide-sensitive quinone reductase activity of the enzyme. However, these mutations did not affect the interaction of NQR with NADH and menadione. It was demonstrated that these conserved cysteine residues are necessary for the correct folding and/or the stability of the NQR complex. Mass and EPR spectroscopy showed that NQR from V. harveyi bears only a 2Fe-2S cluster as a metal-containing prosthetic group.

CHARACTERIZATION OF STABLE BENZOLALPYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA AND POLYDEOXYNUCLEOTIDES

EPA Science Inventory

Bcnzo[a]pyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

Lung toxicity and tumor promotion by hydroxylated derivatives of 2,6-di-tert-butyl-4-methylphenol (BHT) and 2-tert-butyl-4-methyl-6-iso-propylphenol: correlation with quinone methide reactivity.

PubMed

Kupfer, Rene; Dwyer-Nield, Lori D; Malkinson, Alvin M; Thompson, John A

2002-08-01

Acute pulmonary toxicity and tumor promotion by the food additive 2,6-di-tert-butyl-4-methylphenol (BHT) in mice are well documented. These effects have been attributed to either of two quinone methides, 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM) formed through direct oxidation of BHT by pulmonary cytochrome P450 or a quinone methide formed by hydroxylation of a tert-butyl group of BHT (to form BHTOH) followed by oxidation of this metabolite to BHTOH-QM. BHTOH-QM is a more reactive electrophile compared to BHT-QM due to intramolecular interactions of the side-chain hydroxyl with the carbonyl oxygen. To further examine this bioactivation pathway, an analogue of BHTOH was prepared, 2-tert-butyl-6-(1'-hydroxy-1'-methyl)ethyl-4-methylphenol (BPPOH), that is structurally very similar to BHTOH but forms a quinone methide (BPPOH-QM) capable of more efficient intramolecular hydrogen bonding and, therefore, higher electrophilicity than BHTOH-QM. BPPOH-QM was synthesized and its reactivity with water, methanol, and glutathione determined to be >10-fold higher than that of BHTOH-QM. The conversions of BPPOH and BHTOH to quinone methides in lung microsomes from male BALB/cByJ mice were quantitatively similar, but in vivo the former was pneumotoxic at one-half of the dose required for the latter and one-eighth of the dose required for BHT, as determined by increased lung weight:body weight ratios following a single i.p. injection. Similar differences were found in the doses of BHT, BHTOH, or BPPOH required for tumor promotion after a single initiating dose of 3-methylcholanthrene followed by three weekly injections of the phenol. The downregulaton of calpain II, previously shown to accompany lung tumor promotion by BHT and BHTOH, also occurred with BPPOH. The correlation between biologic activities of these phenols and the reactivities of their corresponding quinone methides provides additional support for the role of BHTOH-QM as the principal metabolite responsible for the effects of BHT on mouse lung.

Three-dimensional Structure and Enzymatic Function of Proapoptotic Human p53-inducible Quinone Oxidoreductase PIG3*

PubMed Central

Porté, Sergio; Valencia, Eva; Yakovtseva, Evgenia A.; Borràs, Emma; Shafqat, Naeem; Debreczeny, Judit É.; Pike, Ashley C. W.; Oppermann, Udo; Farrés, Jaume; Fita, Ignacio; Parés, Xavier

2009-01-01

Tumor suppressor p53 regulates the expression of p53-induced genes (PIG) that trigger apoptosis. PIG3 or TP53I3 is the only known member of the medium chain dehydrogenase/reductase superfamily induced by p53 and is used as a proapoptotic marker. Although the participation of PIG3 in the apoptotic pathway is proven, the protein and its mechanism of action were never characterized. We analyzed human PIG3 enzymatic function and found NADPH-dependent reductase activity with ortho-quinones, which is consistent with the classification of PIG3 in the quinone oxidoreductase family. However, the activity is much lower than that of ζ-crystallin, a better known quinone oxidoreductase. In addition, we report the crystallographic structure of PIG3, which allowed the identification of substrate- and cofactor-binding sites, with residues fully conserved from bacteria to human. Tyr-59 in ζ-crystallin (Tyr-51 in PIG3) was suggested to participate in the catalysis of quinone reduction. However, kinetics of Tyr/Phe and Tyr/Ala mutants of both enzymes demonstrated that the active site Tyr is not catalytic but may participate in substrate binding, consistent with a mechanism based on propinquity effects. It has been proposed that PIG3 contribution to apoptosis would be through oxidative stress generation. We found that in vitro activity and in vivo overexpression of PIG3 accumulate reactive oxygen species. Accordingly, an inactive PIG3 mutant (S151V) did not produce reactive oxygen species in cells, indicating that enzymatically active protein is necessary for this function. This supports that PIG3 action is through oxidative stress produced by its enzymatic activity and provides essential knowledge for eventual control of apoptosis. PMID:19349281

NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic β-cells.

PubMed

Gray, Joshua P; Karandrea, Shpetim; Burgos, Delaine Zayasbazan; Jaiswal, Anil A; Heart, Emma A

2016-11-16

NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of β-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H 2 O 2 . Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in β-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in β-cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic β-cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes.

PubMed

Moridani, M Y; Cheon, S S; Khan, S; O'Brien, P J

2002-10-01

A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7-fold increase in plasma transaminase toxicity, an indication of liver toxicity. Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors that also partly prevented cytotoxicity. The 4-HA metabolite formed by NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced toxicity whereas sorbitol, an NADH-generating nutrient, prevented the cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when 4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p-quinone rather than involving oxidative stress.

Differences in the binding of the primary quinone receptor in Photosystem I and reaction centres of Rhodobacter sphaeroides-R26 studied with transient EPR spectroscopy

NASA Astrophysics Data System (ADS)

van der Est, A.; Sieckmann, I.; Lubitz, W.; Stehlik, D.

1995-05-01

The binding of the primary quinone acceptor, Q, in Photosystem I (PS I) and reaction centres (RC's) of Rhodobacter Sphaeroide-R26 in which, the non-heme iron has been replaced by zinc (Zn-bRC's) is studied using transient EPR spectroscopy. In PS I, Q is phylloquinone (vitamin K 1, VK 1) and is referred to as A 1. In Zn-bRC's, it is ubiquinone-10 (UQ 10) and called Q A. Native samples of the two RC's as well as those in which A 1 and Q A have been replaced by perdeuterated napthoquinone (NQ- d6) and duroquinone (DQ- d12) are compared. The spin polarized K-band (24 GHz) spectra of the charge separated state P +.Q -. (P = primary chlorophyll donor) in Zn-bRC's show that substitution of Q A, with NQ- d6 and DQ- d12 does not have a measurable effect on the quinone orientation in the Q A site. In contrast, large differences in the orientation of VK 1, NQ- d6 and DQ- d12 in the A 1 site in PS I are found. In addition, all three quinones in PS I are oriented differently than Q A in Zn-bRC's. Further, the x and y principal values of the g-tensors of VK 1-., NQ -. and DQ -. in PS I are shown to be significantly larger than in frozen alcohol and Zn-bRC's. It is suggested that the differences in the orientation and a g-values of the quinones in the two RC's arise from a weaker binding to the protein in PS I.

NAD(P)H-dependent Quinone Oxidoreductase 1 (NQO1) and Cytochrome P450 Oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic β-cells

PubMed Central

Gray, Joshua P.; Karandrea, Shpetim; Burgos, Delaine Zayasbazan; Jaiswal, Anil A; Heart, Emma A.

2017-01-01

NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of β-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H2O2. Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in β-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in β-cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic β-cells. PMID:27558805

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Designing Light-Activated Charge-Separating Proteins with a Naphthoquinone Amino Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichtenstein, Bruce R.; Bialas, Chris; Cerda, José F.

2015-09-14

The first principles design of manmade redox-protein maquettes is used to clarify the physical/chemical engineering supporting the mechanisms of natural enzymes with a view to recapitulate and surpass natural performance. Herein, we use intein-based protein semisynthesis to pair a synthetic naphthoquinone amino acid (Naq) with histidine-ligated photoactive metal–tetrapyrrole cofactors, creating a 100 μs photochemical charge separation unit akin to photosynthetic reaction centers. By using propargyl groups to protect the redox-active para-quinone during synthesis and assembly while permitting selective activation, we gain the ability to employ the quinone amino acid redox cofactor with the full set of natural amino acids inmore » protein design. Direct anchoring of quinone to the protein backbone permits secure and adaptable control of intraprotein electron-tunneling distances and rates.« less

Activity-guided isolation of the chemical constituents of Muntingia calabura using a quinone reductase induction assay.

PubMed

Su, Bao-Ning; Jung Park, Eun; Vigo, Jose Schunke; Graham, James G; Cabieses, Fernando; Fong, Harry H S; Pezzuto, John M; Kinghorn, A Douglas

2003-06-01

Activity-guided fractionation of an EtOAc-soluble extract of the leaves of Muntingia calabura collected in Peru, using an in vitro quinone reductase induction assay with cultured Hepa 1c1c7 (mouse hepatoma) cells, resulted in the isolation of a flavanone with an unsubstituted B-ring, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone (5), as well as 24 known compounds, which were mainly flavanones and flavones. The structure including absolute stereochemistry of compound 5 was determined by spectroscopic (HRMS, 1D and 2D NMR, and CD spectra) methods. Of the isolates obtained, in addition to 5, (2S)-5-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, 4,2',4'-trihydroxychalcone, 7-hydroxyisoflavone and 7,3',4'-trimethoxyisoflavone were found to induce quinone reductase activity.

Absorption spectrometric study of charge transfer complex formation between 4-acetamidophenol (paracetamol) and a series of quinones including Vitamin K 3

NASA Astrophysics Data System (ADS)

Saha, Avijit; Mukherjee, Asok K.

2004-07-01

The formation of charge transfer (CT) complexes of 4-acetamidophenol (commonly called 'paracetamol') and a series of quinones (including Vitamin K 3) has been studied spectrophotometrically in ethanol medium. The vertical ionisation potential of paracetamol and the degrees of charge transfer of the complexes in their ground state has been estimated from the trends in the charge transfer bands. The oscillator and transition dipole strengths of the complexes have been determined from the CT absorption spectra at 298 K. The complexes have been found by Job's method of continuous variation to have the uncommon 2:1 (paracetamol:quinone) stoichiometry in each case. The enthalpies and entropies of formation of the complexes have been obtained by determining their formation constants at five different temperatures.

Bimolecular Rate Constants for FAD-Dependent Glucose Dehydrogenase from Aspergillus terreus and Organic Electron Acceptors.

PubMed

Tsuruoka, Nozomu; Sadakane, Takuya; Hayashi, Rika; Tsujimura, Seiya

2017-03-10

The flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) from Aspergillus species require suitable redox mediators to transfer electrons from the enzyme to the electrode surface for the application of bioelectrical devices. Although several mediators for FAD-GDH are already in use, they are still far from optimum in view of potential, kinetics, sustainability, and cost-effectiveness. Herein, we investigated the efficiency of various phenothiazines and quinones in the electrochemical oxidation of FAD-GDH from Aspergillus terreus . At pH 7.0, the logarithm of the bimolecular oxidation rate constants appeared to depend on the redox potentials of all the mediators tested. Notably, the rate constant of each molecule for FAD-GDH was approximately 2.5 orders of magnitude higher than that for glucose oxidase from Aspergillus sp. The results suggest that the electron transfer kinetics is mainly determined by the formal potential of the mediator, the driving force of electron transfer, and the electron transfer distance between the redox active site of the mediator and the FAD, affected by the steric or chemical interactions. Higher k ₂ values were found for ortho-quinones than for para-quinones in the reactions with FAD-GDH and glucose oxidase, which was likely due to less steric hindrance in the active site in the case of the ortho-quinones.

Quinonoid constituents as contact sensitisers in Australian blackwood (Acacia melanoxylon RBR).

PubMed Central

Hausen, B M; Schmalle, H

1981-01-01

Australian blackwood (Acacia melanoxylon RBR) is a valuable commercial timber that since 1925 has been incriminated as being injurious to health. In addition to toxic effects numerous cases of allergic contact dermatitis and bronchial asthma have been observed in woodworkers. Several constituents have been identified in recent years, but none of them could be considered as aetiological factors. Sensitizing experiments performed with blackwood heartwood extracts corroborated the described sensitising properties. Chemical studies showed the occurrence of two or possibly three quinones that produced positive skin responses in the sensitised guinea pigs. The main contact allergens were isolated and identified by x-ray analysis. The first, a yellow quinone, was identified as 2,6-dimethoxy-1,4-benzoquinone while the second, a red quinone, has the structure of 6-methoxy-2-methyl-3,5-dihydrobenzofurano-4,7-dion and was named acamelin. Whereas 2, 6-dimethoxy-p-benzoquinone is already known from natural sources, acamelin is new and belongs to the rate group of naturally occurring furanoquinones. Though the obtained sensitising capacity of A melanoxylon RBR in respect of its quinones is not high, it should be considered as a possible source of allergic contact dermatitis, especially as greater amounts of Australian blackwood may enter European countries in the near future. PMID:7236533

A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial cells.

PubMed

Kogan, Natalya M; Blázquez, Cristina; Alvarez, Luis; Gallily, Ruth; Schlesinger, Michael; Guzmán, Manuel; Mechoulam, Raphael

2006-07-01

Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compound a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice. For evaluation of the antiangiogenic action of cannabinoid quinones, collagen-embedded rat aortic ring assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells, human cDNA microarrays and polymerase chain reaction were used. Immunostaining with anti-CD31 of tumors grown in nude mice served to indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly antiangiogenic, significantly inhibiting angiogenesis at concentrations as low as 300 nM. HU-331 inhibited angiogenesis by directly inducing apoptosis of vascular endothelial cells without changing the expression of pro- and antiangiogenic cytokines and their receptors. A significant decrease in the total area occupied by vessels in HU-331-treated tumors was also observed. These data lead us to consider HU-331 to have high potential as a new antiangiogenic and anticancer drug.

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.

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.

Carbon nanotube-supported Au-Pd alloy with cooperative effect of metal nanoparticles and organic ketone/quinone groups as a highly efficient catalyst for aerobic oxidation of amines.

PubMed

Deng, Weiping; Chen, Jiashu; Kang, Jincan; Zhang, Qinghong; Wang, Ye

2016-05-21

Functionalised carbon nanotube (CNT)-supported Au-Pd alloy nanoparticles were highly efficient catalysts for the aerobic oxidation of amines. We achieved the highest turnover frequencies (>1000 h(-1)) for the oxidative homocoupling of benzylamine and the oxidative dehydrogenation of dibenzylamine. We discovered a cooperative effect between Au-Pd nanoparticles and ketone/quinone groups on CNTs.

Unprecedent aminophysalin from Physalis angulata.

PubMed

Men, Rui-Zhi; Li, Ning; Ding, Wan-Jing; Hu, Zhi-Juan; Ma, Zhong-Jun; Cheng, Lin

2014-10-01

The 95% ethanol extract of the whole plant of Physalis angulata Linn. afforded one new skeletal physalin named aminophysalin A (1) and one new naturally occurring 5β-hydroxy-6a-chloro-5,6-dihydrophysalin B (2), together with five known physalins (3-7). Their structures were elucidated through MS, IR, NMR spectroscopy analyses and X-ray crystallography. Aminophysalin A (1) had an absolutely unusual structural feature in the chemistry of physalins with a nitrogen atom. Compounds 1-7 were evaluated for quinone reductase activities in hepa 1c1c7 cells. Physalin H (6) showed strong quinone reductase induction activity with IR (Induction ratio, QR induction activity) value of 3.74±0.02, using 4-bromoflavone as a positive control substance (2.17±0.01, 10 μg/mL), while compounds 1, 2, 3, 5 showed weak quinone reductase induction activity. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

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.

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

PubMed Central

Jamieson, D; Tung, A T Y; Knox, R J; Boddy, A V

2006-01-01

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species. PMID:17031400

Antioxidant and drug detoxification potential of aqueous extract of Annona senegalensis leaves in carbon tetrachloride-induced hepatocellular damage.

PubMed

Ajboye, Taofeek O; Yakubu, Musa T; Salau, Amadu K; Oladiji, Adenike T; Akanji, Musbau A; Okogun, Joseph I

2010-12-01

 Despite the myriad uses of Annona senegalensis Pers. (Annonaceae) leaves in folklore medicine of Nigeria, the basis is yet to be substantiated by scientific investigations.  To investigate the antioxidant (in vitro and in vivo) and drug detoxification potential of aqueous extract of A. senegalensis leaves in CCl₄-induced hepatocellular damage.  In vitro antioxidant activity of the aqueous extract of A. senegalensis leaves was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H₂O₂, superoxide ion, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and ferric ion models while in vivo antioxidant and drug detoxification activities of the extract at 100, 200, and 400 mg/kg body weight were done by assaying the levels of enzymic and non-enzymic indices in CCl₄-induced hepatocellular damage.  The extract at 1 mg/mL scavenged DPPH, H₂O₂, superoxide ion, and ABTS radicals, whereas ferric ion was significantly (P <0.05) reduced. The levels of alkaline and acid phosphatases, alanine and aspartate aminotransferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, reduced glutathione, vitamins C and E, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced):Quinone oxidoreductase, uridyl diphosphoglucuronyl transferase, malondialdehyde, and lipid hydroperoxide that decreased in CCl₄ treated animals were significantly attenuated by the extract in a manner similar to the animals treated with the reference drug.  The ability of the aqueous extract of A. senegalensis leaves to scavenge free radicals in vitro and reversal of CCl₄-induced hepatocellular damage in rats suggest antioxidant and drug detoxification activities. Overall, this study has justified the rationale behind some of the medicinal uses of the plant in folklore medicine of Nigeria.

Eleusine indica L. possesses antioxidant activity and precludes carbon tetrachloride (CCl₄)-mediated oxidative hepatic damage in rats.

PubMed

Iqbal, Mohammad; Gnanaraj, Charles

2012-07-01

The purpose of this study was to evaluate the ability of aqueous extract of Eleusine indica to protect against carbon tetrachloride (CCl₄)-induced hepatic injury in rats. The antioxidant activity of E. indica was evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The total phenolic content of E. indica was also determined. Biochemical parameters [e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), glutathione (GSH), catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and quinone reductase] were used to evaluate hepatic damage in animals pretreated with E. indica and intoxicated with CCl₄. CCl₄-mediated hepatic damage was also evaluated by histopathologically. E. indica extract was able to reduce the stable DPPH level in a dose-dependent manner. The half maximal inhibitory concentration (IC₅₀) value was 2350 μg/ml. Total phenolic content was found to be 14.9 ± 0.002 mg/g total phenolic expressed as gallic acid equivalent per gram of extract. Groups pretreated with E. indica showed significantly increased activity of antioxidant enzymes compared to the CCl₄-intoxicated group (p < 0.05). The increased levels of serum ALT and AST were significantly prevented by E. indica pretreatment (p < 0.05). The extent of MDA formation due to lipid peroxidation was significantly reduced (p < 0.05), and reduced GSH was significantly increased in a dose-dependently manner (p < 0.05) in the E. indica-pretreated groups as compared to the CCl₄-intoxicated group. The protective effect of E. indica was further evident through decreased histopathological alterations in the liver. The results of our study indicate that the hepatoprotective effects of E. indica might be ascribable to its antioxidant and free radical scavenging property.

Intrinsic chemiluminescence production from the degradation of haloaromatic pollutants during environmentally-friendly advanced oxidation processes: Mechanism, structure-activity relationship and potential applications.

PubMed

Zhu, Benzhan; Shen, Chen; Gao, Huiying; Zhu, Liya; Shao, Jie; Mao, Li

2017-12-01

The ubiquitous distribution of halogenated aromatic compounds (XAr) coupled with their carcinogenicity has raised public concerns on their potential risks to both human health and the ecosystem. Recently, advanced oxidation processes (AOPs) have been considered as an "environmentally-friendly" technology for the remediation and destruction of such recalcitrant and highly toxic XAr. During our study on the mechanism of metal-independent production of hydroxyl radicals (OH) by halogenated quinones and H 2 O 2 , we found, unexpectedly, that an unprecedented OH-dependent two-step intrinsic chemiluminescene (CL) can be produced by H 2 O 2 and tetrachloro-p-benzoquinone, the major carcinogenic metabolite of the widely used wood preservative pentachlorophenol. Further investigations showed that, in all OH-generating systems, CL can also be produced not only by pentachlorophenol and all other halogenated phenols, but also by all XAr tested. A systematic structure-activity relationship study for all 19 chlorophenolic congeners showed that the CL increased with an increasing number of Cl-substitution in general. More importantly, a relatively good correlation was observed between the formation of quinoid/semiquinone radical intermediates and CL generation. Based on these results, we propose that OH-dependent formation of quinoid intermediates and electronically excited carbonyl species is responsible for this unusual CL production; and a rapid, sensitive, simple, and effective CL method was developed not only to detect and quantify trace amount of XAr, but also to provide useful information for predicting the toxicity or monitoring real-time degradation kinetics of XAr. These findings may have broad chemical, environmental and biological implications for future studies on halogenated aromatic persistent organic pollutants. Copyright © 2017. Published by Elsevier B.V.

Nano-MnO2-mediated transformation of triclosan with humic molecules present: kinetics, products, and pathways.

PubMed

Sun, Kai; Li, Shunyao; Waigi, Michael Gatheru; Huang, Qingguo

2018-05-01

It has been shown that manganese dioxide (MnO 2 ) can mediate transformation of phenolic contaminants to form phenoxyl radical intermediates, and subsequently, these intermediates intercouple to form oligomers via covalent binding. However, the reaction kinetics and transformation mechanisms of phenolic contaminants with humic molecules present in nano-MnO 2 -mediated systems were still unclear. In this study, it was proven that nano-MnO 2 were effective in transforming triclosan under acidic conditions (pH 3.5-5.0) during manganese reduction, and the apparent pseudo first-order kinetics rate constants (k = 0.0599-1.5314 h -1 ) increased as the pH decreased. In particular, the transformation of triclosan by nano-MnO 2 was enhanced in the presence of low-concentration humic acid (1-10 mg L -1 ). The variation in the absorption of humic molecules at 275 nm supported possible covalent binding between humic molecules and triclosan in the nano-MnO 2 -mediated systems. A total of four main intermediate products were identified by high-resolution mass spectrometry (HRMS), regardless of humic molecules present in the systems or not. These products correspond to a suite of radical intercoupling reactions (dimers and trimers), ether cleavage (2,4-dichlorophenol), and oxidation to quinone-like products, triggered by electron transfer from triclosan molecules to nano-MnO 2 . A possible reaction pathway in humic acid solutions, including homo-coupling, decomposition, oxidation, and cross-coupling, was proposed. Our findings provide valuable information regarding the environmental fate and transformation mechanism of triclosan by nano-MnO 2 in complex water matrices.

Degradation of oxidatively denatured proteins in Escherichia coli.

PubMed

Davies, K J; Lin, S W

1988-01-01

When exposed to oxidative stress, by oxygen radicals or H2O2, E. coli exhibited decreased growth, decreased protein synthesis, and dose-dependent increases in protein degradation. The quinone menadione induced proteolysis when cells were incubated in air, but was not effective when cells were incubated without oxygen. Anaerobically grown cells also exhibited significantly lower proteolytic capacity than did cells that were grown aerobically. Xanthine plus xanthine oxidase (which generate O2- and H2O2) caused a stimulation of proteolysis which was inhibitable by catalase, but not by superoxide dismutase: Indicating that H2O2 was responsible for the increased protein degradation. Indeed, H2O2 alone was effective in inducing increased intracellular proteolysis. Two-dimensional polyacrylamide gel electrophoresis of [3H]leucine labeled E. coli revealed greater than 50% decreases in the concentrations of 10-15 cell proteins following H2O2 or menadione exposure, while several other proteins were less severely affected. To test for the presence of soluble proteases, we prepared cell-free extracts of E. coli and incubated them with radio-labeled protein substrates. E. coli extracts degraded casein and globin polypeptides at rapid rates but showed little activity with native proteins such as superoxide dismutase, hemoglobin, bovine serum albumin, or catalase. When these same proteins were denatured by exposure to oxygen radicals or H2O2, however, they became excellent substrates for degradation in E. coli extracts. Studies with albumin revealed correlations greater than 0.95 between the degree of oxidative denaturation and proteolytic susceptibility. Pretreatment of E. coli with menadione or H2O2 did not increase the proteolytic capacity of cell extracts; indicating that neither protease activation, nor protease induction were required.(ABSTRACT TRUNCATED AT 250 WORDS)

1,6-Conjugate addition of zinc alkyls to para-quinone methides in a continuous-flow microreactor.

PubMed

Jadhav, Abhijeet S; Anand, Ramasamy Vijaya

2016-12-20

An efficient method for the synthesis of alkyl diarylmethanes through the 1,6-conjugate addition of dialkylzinc reagents to para-quinone methides (p-QMs) has been developed under continuous flow conditions using a microreactor. This protocol allows to access unsymmetrical alkyl diarylmethanes in moderate to excellent yields using a wide range of p-QMs and dialkylzinc reagents. Interestingly, this transformation worked well without the requirement of a catalyst.

Synergistic electron transfer effect-based signal amplification strategy for the ultrasensitive detection of dopamine.

PubMed

Lu, Qiujun; Chen, Xiaogen; Liu, Dan; Wu, Cuiyan; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

2018-05-15

The selective and sensitive detection of dopamine (DA) is of great significance for the identification of schizophrenia, Huntington's disease, and Parkinson's disease from the perspective of molecular diagnostics. So far, most of DA fluorescence sensors are based on the electron transfer from the fluorescence nanomaterials to DA-quinone. However, the limited electron transfer ability of the DA-quinone affects the level of detection sensitivity of these sensors. In this work, based on the DA can reduce Ag + into AgNPs followed by oxidized to DA-quinone, we developed a novel silicon nanoparticles-based electron transfer fluorescent sensor for the detection of DA. As electron transfer acceptor, the AgNPs and DA-quinone can quench the fluorescence of silicon nanoparticles effectively through the synergistic electron transfer effect. Compared with traditional fluorescence DA sensors, the proposed synergistic electron transfer-based sensor improves the detection sensitivity to a great extent (at least 10-fold improvement). The proposed sensor shows a low detection limit of DA, which is as low as 0.1 nM under the optimal conditions. This sensor has potential applicability for the detection of DA in practical sample. This work has been demonstrated to contribute to a substantial improvement in the sensitivity of the sensors. It also gives new insight into design electron transfer-based sensors. Copyright © 2018. Published by Elsevier B.V.

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.

The degradation of three-ringed polycyclic aromatic hydrocarbons by wood-inhabiting fungus Pleurotus ostreatus and soil-inhabiting fungus Agaricus bisporus.

PubMed

Pozdnyakova, Natalia; Dubrovskaya, Ekaterina; Chernyshova, Marina; Makarov, Oleg; Golubev, Sergey; Balandina, Svetlana; Turkovskaya, Olga

2018-05-01

The degradation of two isomeric three-ringed polycyclic aromatic hydrocarbons by the white rot fungus Pleurotus ostreatus D1 and the litter-decomposing fungus Agaricus bisporus F-8 was studied. Despite some differences, the degradation of phenanthrene and anthracene followed the same scheme, forming quinone metabolites at the first stage. The further fate of these metabolites was determined by the composition of the ligninolytic enzyme complexes of the fungi. The quinone metabolites of phenanthrene and anthracene produced in the presence of only laccase were observed to accumulate, whereas those formed in presence of laccase and versatile peroxidase were metabolized further to form products that were further included in basal metabolism (e.g. phthalic acid). Laccase can catalyze the initial attack on the PAH molecule, which leads to the formation of quinones, and that peroxidase ensures their further oxidation, which eventually leads to PAH mineralization. A. bisporus, which produced only laccase, metabolized phenanthrene and anthracene to give the corresponding quinones as the dominant metabolites. No products of further utilization of these compounds were detected. Thus, the fungi's affiliation with different ecophysiological groups and their cultivation conditions affect the composition and dynamics of production of the ligninolytic enzyme complex and the completeness of PAH utilization. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of Horminum pyrenaicum in Human PBMC

PubMed Central

Becker, K.; Schwaiger, S.; Waltenberger, B.; Pezzei, C. K.; Schennach, H.

2018-01-01

Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ-) dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root of Horminum (H.) pyrenaicum L. (syn. Dragon's mouth), the only representative of the monophyletic genus Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product), two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone) and two abeo 18 (4 → 3) abietane diterpene quinones (agastol and its 15,16-dehydro-derivative) could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis. PMID:29576845

Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity.

PubMed

de Molfetta, Fábio Alberto; de Freitas, Renato Ferreira; da Silva, Albérico Borges Ferreira; Montanari, Carlos Alberto

2009-10-01

In this work, two different docking programs were used, AutoDock and FlexX, which use different types of scoring functions and searching methods. The docking poses of all quinone compounds studied stayed in the same region in the trypanothione reductase. This region is a hydrophobic pocket near to Phe396, Pro398 and Leu399 amino acid residues. The compounds studied displays a higher affinity in trypanothione reductase (TR) than glutathione reductase (GR), since only two out of 28 quinone compounds presented more favorable docking energy in the site of human enzyme. The interaction of quinone compounds with the TR enzyme is in agreement with other studies, which showed different binding sites from the ones formed by cysteines 52 and 58. To verify the results obtained by docking, we carried out a molecular dynamics simulation with the compounds that presented the highest and lowest docking energies. The results showed that the root mean square deviation (RMSD) between the initial and final pose were very small. In addition, the hydrogen bond pattern was conserved along the simulation. In the parasite enzyme, the amino acid residues Leu399, Met400 and Lys402 are replaced in the human enzyme by Met406, Tyr407 and Ala409, respectively. In view of the fact that Leu399 is an amino acid of the Z site, this difference could be explored to design selective inhibitors of TR.

The 2013 Discovery Award from the Society for Free Radical Biology and Medicine: Selected Discoveries from the Butterfield Laboratory of Oxidative Stress and Its Sequelae in Brain in Cognitive Disorders Exemplified by Alzheimer Disease and Chemotherapy Induced Cognitive Impairment

PubMed Central

Butterfield, D. Allan

2014-01-01

This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of: protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called “chemobrain” by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, Apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a pro-inflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent with the clinical presentation, biochemistry, and pathology of this disorder. To the author's knowledge this is the only plausible and self-consistent mechanism to explain CICI. These two different disorders of the CNS affect millions of persons worldwide. Both AD and CICI share free radical-mediated oxidative stress in brain, but the source of oxidative stress is not the same. Continued research is necessary to better understand both AD and CICI. The discoveries about these disorders from the Butterfield laboratory that led to the 2013 Discovery Award from the Society of Free Radical and Medicine provides a significant foundation from which this future research can be launched. PMID:24996204

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 this report is to bring under wider attention the apparently widespread phenomenon of two-plateau Michaelis-Menten plots. PMID:22952804

Metabolic activation of 3-hydroxyanisole by isolated rat hepatocytes.

PubMed

Moridani, Majid Y; Cheon, Sophia S; Khan, Sumsullah; O'Brien, Peter J

2003-01-06

A tyrosinase-directed therapeutic approach for malignant melanoma therapy uses the depigmenting phenolic agents such as 4-hydroxyanisole (4-HA) to form cytotoxic o-quinones. However, renal and hepatic toxicity was reported as side effects in a recent 4-HA clinical trial. In search of novel therapeutics, the cytotoxicity of the isomers 4-HA, 3-HA and 2-HA were investigated. In the following, the order of the HAs induced hepatotoxicity in mice, as measured by increased in vivo plasma transaminase activity, or in isolated rat hepatocytes, as measured by trypan blue exclusion, was 3-HA > 2-HA > 4-HA. Hepatocyte GSH depletion preceded HA induced cytotoxicity and a 4-MC-SG conjugate was identified by LC/MS/MS mass spectrometry analysis when 3-HA was incubated with NADPH/microsomes/GSH. 3-HA induced hepatocyte GSH depletion or GSH depletion when 3-HA was incubated with NADPH/microsomes was prevented by CYP 2E1 inhibitors. Dicumarol (an NAD(P)H: quinone oxidoreductase inhibitor) potentiated 3-HA- or 4-methoxycatechol (4-MC) induced toxicity whereas sorbitol (an NADH generating nutrient) greatly prevented cytotoxicity indicating a quinone-mediated cytotoxic mechanism. Ethylendiamine (an o-quinone trap) largely prevented 3-HA and 4-MC-induced cytotoxicity indicating that o-quinone was involved in cytotoxicity. Dithiothreitol (DTT) greatly reduced 3-HA and 4-MC induced toxicity. The ferric chelator deferoxamine slightly decreased 3-HA and 4-MC induced cytotoxicity whereas the antioxidants pyrogallol or TEMPOL greatly prevented the toxicity suggesting that oxidative stress contributed to 3-HA induced cytotoxicity. In summary, ring hydroxylation but not O-demethylation/epoxidation seems to be the bioactivation pathway for 3-HA in rat liver. The cytotoxic mechanism for 3-HA and its metabolite 4-MC likely consists cellular protein alkylation and oxidative stress. These results suggest that 3-HA is not suitable for treatment of melanoma. Copyright 2002 Elsevier Science B.V.

Conformational differences between the methoxy groups of QA and QB site ubisemiquinones in bacterial reaction centers: a key role for methoxy group orientation in modulating ubiquinone redox potential.

PubMed

Taguchi, Alexander T; O'Malley, Patrick J; Wraight, Colin A; Dikanov, Sergei A

2013-07-09

Ubiquinone is an almost universal, membrane-associated redox mediator. Its ability to accept either one or two electrons allows it to function in critical roles in biological electron transport. The redox properties of ubiquinone in vivo are determined by its environment in the binding sites of proteins and by the dihedral angle of each methoxy group relative to the ring plane. This is an attribute unique to ubiquinone among natural quinones and could account for its widespread function with many different redox complexes. In this work, we use the photosynthetic reaction center as a model system for understanding the role of methoxy conformations in determining the redox potential of the ubiquinone/semiquinone couple. Despite the abundance of X-ray crystal structures for the reaction center, quinone site resolution has thus far been too low to provide a reliable measure of the methoxy dihedral angles of the primary and secondary quinones, QA and QB. We performed 2D ESEEM (HYSCORE) on isolated reaction centers with ubiquinones (13)C-labeled at the headgroup methyl and methoxy substituents, and have measured the (13)C isotropic and anisotropic components of the hyperfine tensors. Hyperfine couplings were compared to those derived by DFT calculations as a function of methoxy torsional angle allowing estimation of the methoxy dihedral angles for the semiquinones in the QA and QB sites. Based on this analysis, the orientation of the 2-methoxy groups are distinct in the two sites, with QB more out of plane by 20-25°. This corresponds to an ≈50 meV larger electron affinity for the QB quinone, indicating a substantial contribution to the experimental difference in redox potentials (60-75 mV) of the two quinones. The methods developed here can be readily extended to ubiquinone-binding sites in other protein complexes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Lele; Manbeck, Gerald F.; Kowalczyk, Marta

Ruthenium complexes with proton-responsive ligands [Ru(tpy)(nDHBP)(NCCH 3)](CF 3SO 3) 2 (tpy = 2,2':6',2"-terpyridine; nDHBP = n,n'-dihydroxy-2,2'-bipyridine, n = 4 or 6) were examined in this study for reductive chemistry and as catalysts for CO 2 reduction. Electrochemical reduction of [Ru(tpy)(nDHBP)(NCCH 3)] 2+ generates deprotonated species through interligand electron transfer in which the initially formed tpy radical anion reacts with a proton source to produce singly and doubly deprotonated complexes that are identical to those obtained by base titration. A third reduction (i.e., reduction of [Ru(tpy)(nDHBP–2H +)] 0) triggers catalysis of CO 2 reduction; however, the catalytic efficiency is strikingly lowermore » than that of unsubstituted [Ru(tpy)(bpy)(NCCH 3)] 2+ (bpy = 2,2'-bipyridine). Cyclic voltammetry, bulk electrolysis, and spectroelectrochemical infrared experiments suggest the reactivity of CO 2 at both the Ru center and the deprotonated quinone-type ligand. Lastly, the Ru carbonyl formed by the intermediacy of a metallocarboxylic acid is stable against reduction, and mass spectrometry analysis of this product indicates the presence of two carbonates formed by the reaction of DHBP–2H + with CO 2.« less

Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method.

PubMed

Ito, Shosuke; Kikuta, Marina; Koike, Shota; Szewczyk, Grzegorz; Sarna, Michal; Zadlo, Andrzej; Sarna, Tadeusz; Wakamatsu, Kazumasa

2016-05-01

Eumelanin photoprotects pigmented tissues from ultraviolet (UV) damage. However, UVA-induced tanning seems to result from the photooxidation of preexisting melanin and does not contribute to photoprotection. We investigated the mechanism of UVA-induced degradation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-melanin taking advantage of its solubility in a neutral buffer and using a differential spectrophotometric method to detect subtle changes in its structure. Our methodology is suitable for examining the effects of various agents that interact with reactive oxygen species (ROS) to determine how ROS is involved in the UVA-induced oxidative modifications. The results show that UVA radiation induces the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in eumelanin, which is then cleaved to form a photodegraded, pyrrolic moiety and finally to form free pyrrole-2,3,5-tricarboxylic acid. The possible involvement of superoxide radical and singlet oxygen in the oxidation was suggested. The generation and quenching of singlet oxygen by DHICA-melanin was confirmed by direct measurements of singlet oxygen phosphorescence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acetylacetone as an efficient electron shuttle for concerted redox conversion of arsenite and nitrate in the opposite direction.

PubMed

Chen, Zhihao; Song, Xiaojie; Zhang, Shujuan; Wu, Bingdang; Zhang, Guoyang; Pan, Bingcai

2017-11-01

The redox conversion of arsenite and nitrate has direct effects on their potential environment risks. Due to the similar reduction potentials, there are few technologies that can simultaneously oxidize arsenite and reduce nitrate in one process. Here, we demonstrate that a diketone-mediated photochemical process could efficiently do this. A combined experimental and theoretical investigation was conducted to elucidate the mechanisms behind the redox conversion in the UV/acetylacetone (AA) process. Our key finding is that UV irradiation significantly changed the redox potential of AA. The excited AA, 3 (AA)*, acted as a semiquinone radical-like electron shuttle. For arsenite oxidation, the efficiency of 3 (AA)* was 1-2 orders of magnitude higher than those of quinone-type electron shuttles, whereas the consumption of AA was 2-4 orders of magnitude less than those of benzonquinones. The oxidation of arsenite and reduction of nitrate could be both accelerated when they existed together in UV/AA process. The results indicate that small diketones are some neglected but potent electron shuttles of great application potential in regulating aquatic redox reactions with the combination of UV irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of Estrogen-Depurinating DNA Adducts by Sulforaphane for Breast Cancer

DTIC Science & Technology

2014-12-01

adducts. NQO1 reduces CE-3,4- 5 quinones back to catechols and GST catalyzes the conjugation of CE-3,4-quinones with glutathione, whereas COMT ... COMT , GSTA1 and β-actin (Sigma) antibodies were made in blocking solution (5% non-fat dry milk in Tris-buffered saline). The blots were incubated...other genes known to influence E2 metabolism, namely CYP1B1 and COMT , were observed (Figure 4A). These inductions exhibited a dose response, with

Diels-Alder reactions of 12-hydroxy-9(10®20)-5aH-abeo-abieta-1(10),8(9),12(13)-triene-11,14-dione.

PubMed

Majetich, George; Zhang, Yong; Tian, Xinrong; Zou, Ge; Li, Yang; Wang, Yangyang; Hu, Shougang; Huddleston, Eric

2013-06-14

12-Hydroxy-9(10-->20)-5aH-abeo-abieta-1(10),8(9),12(13)-triene-11,14-dione (quinone 2) served as the dienophile in numerous intermolecular Diels-Alder reactions. These cycloadditions were conducted either thermally (including microwave heating) or with Lewis acid activation. While most dienes reacted with quinone 2 in good chemical yield, others were incompatible under the experimental conditions used.

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.

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. © 2013 Wiley Periodicals, Inc.

Lignin Modification for Biopolymer/Conjugated Polymer Hybrids as Renewable Energy Storage Materials.

PubMed

Nilsson, Ting Yang; Wagner, Michal; Inganäs, Olle

2015-12-07

Lignin derivatives, which arise as waste products from the pulp and paper industry and are mainly used for heating, can be used as charge storage materials. The charge storage function is a result of the quinone groups formed in the lignin derivative. Herein, we modified lignins to enhance the density of such quinone groups by covalently linking monolignols and quinones through phenolation. The extra guaiacyl, syringyl, and hydroquinone groups introduced by phenolation of kraft lignin derivatives were monitored by (31) P nuclear magnetic resonance and size exclusion chromatography. Electropolymerization in ethylene glycol/tetraethylammonium tosylate electrolyte was used to synthesize the kraft lignin/polypyrrole hybrid films. These modifications changed the phenolic content of the kraft lignin with attachment of hydroquinone units yielding the highest specific capacity (around 70 mA h g(-1) ). The modification of softwood and hardwood lignin derivatives yielded 50 % and 23 % higher charge capacity than the original lignin, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

15N and13C NMR investigation of hydroxylamine-derivatized humic substances

USGS Publications Warehouse

Thorn, K.A.; Arterburn, J.B.; Mikita, M.A.

1992-01-01

Five fulvic and humic acid samples of diverse origins were derivatized with 15N-labeled hydroxylamine and analyzed by liquid-phase 15N NMR spectrometry. The 15N NMR spectra indicated that hydroxylamine reacted similarly with all samples and could discriminate among carbonyl functional groups. Oximes were the major derivatives; resonances attributable to hydroxamic acids, the reaction products of hydroxylamine with esters, and resonances attributable to the tautomeric equilibrium position between the nitrosophenol and monoxime derivatives of quinones, the first direct spectroscopic evidence for quinones, also were evident. The 15N NMR spectra also suggested the presence of nitriles, oxazoles, oxazolines, isocyanides, amides, and lactams, which may all be explained in terms of Beckmann reactions of the initial oxime derivatives. INEPT and ACOUSTIC 15N NMR spectra provided complementary information on the derivatized samples. 13C NMR spectra of derivatized samples indicated that the ketone/quinone functionality is incompletely derivatized with hydroxylamine. ?? 1991 American Chemical Society.

Biosynthesis of actinorhodin and related antibiotics: discovery of alternative routes for quinone formation encoded in the act gene cluster.

PubMed

Okamoto, Susumu; Taguchi, Takaaki; Ochi, Kozo; Ichinose, Koji

2009-02-27

All known benzoisochromanequinone (BIQ) biosynthetic gene clusters carry a set of genes encoding a two-component monooxygenase homologous to the ActVA-ORF5/ActVB system for actinorhodin biosynthesis in Streptomyces coelicolor A3(2). Here, we conducted molecular genetic and biochemical studies of this enzyme system. Inactivation of actVA-ORF5 yielded a shunt product, actinoperylone (ACPL), apparently derived from 6-deoxy-dihydrokalafungin. Similarly, deletion of actVB resulted in accumulation of ACPL, indicating a critical role for the monooxygenase system in C-6 oxygenation, a biosynthetic step common to all BIQ biosyntheses. Furthermore, in vitro, we showed a quinone-forming activity of the ActVA-ORF5/ActVB system in addition to that of a known C-6 monooxygenase, ActVA-ORF6, by using emodinanthrone as a model substrate. Our results demonstrate that the act gene cluster encodes two alternative routes for quinone formation by C-6 oxygenation in BIQ biosynthesis.

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.

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Does menaquinone participate in brain astrocyte electron transport?

PubMed

Lovern, Douglas; Marbois, Beth

2013-10-01

Quinone compounds act as membrane resident carriers of electrons between components of the electron transport chain in the periplasmic space of prokaryotes and in the mitochondria of eukaryotes. Vitamin K is a quinone compound in the human body in a storage form as menaquinone (MK); distribution includes regulated amounts in mitochondrial membranes. The human brain, which has low amounts of typical vitamin K dependent function (e.g., gamma carboxylase) has relatively high levels of MK, and different regions of brain have different amounts. Coenzyme Q (Q), is a quinone synthesized de novo, and the levels of synthesis decline with age. The levels of MK are dependent on dietary intake and generally increase with age. MK has a characterized role in the transfer of electrons to fumarate in prokaryotes. A newly recognized fumarate cycle has been identified in brain astrocytes. The MK precursor menadione has been shown to donate electrons directly to mitochondrial complex III. Vitamin K compounds function in the electron transport chain of human brain astrocytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model.

PubMed

Zhao, Lei; Gong, Neng; Liu, Meng; Pan, Xiaoli; Sang, Shaoming; Sun, Xiaojing; Yu, Zhe; Fang, Qi; Zhao, Na; Fei, Guoqiang; Jin, Lirong; Zhong, Chunjiu; Xu, Tianle

2014-12-01

Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone. Copyright © 2014 Elsevier Inc. All rights reserved.

Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea

PubMed Central

Duszenko, Nikolas

2017-01-01

ABSTRACT Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri. The concentration of MPh suggests the cell membrane of M. acetivorans, but not of M. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans. Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans, but not Methanosarcina barkeri, has electrically quantized membranes. Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale. PMID:28710268

Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea.

PubMed

Duszenko, Nikolas; Buan, Nicole R

2017-09-15

Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri The concentration of MPh suggests the cell membrane of M. acetivorans , but not of M. barkeri , is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans , but not Methanosarcina barkeri , has electrically quantized membranes. Escherichia coli , a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale. Copyright © 2017 American Society for Microbiology.

In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA (‘ecstasy') and p-chloroamphetamine but not the degeneration following fenfluramine

PubMed Central

Colado, M I; O'Shea, E; Granados, R; Murray, T K; Green, A R

1997-01-01

Administration of 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy') to several species results in a long lasting neurotoxic degeneration of 5-hydroxytryptaminergic neurones in several regions of the brain. We have now investigated whether this degeneration is likely to be the result of free radical-induced damage. Free radical formation can be assessed by measuring the formation of 2,3- and 2,5-dihydroxybenzoic acid (2,3-DHBA and 2,5-DHBA) from salicylic acid. An existing method involving implantation of a probe into the hippocampus and in vivo microdialysis was modified and validated. Administration of MDMA (15 mg kg−1, i.p.) to Dark Agouti (DA) rats increased the formation of 2,3-DHBA (but not 2,5-DHBA) for at least 6 h. Seven days after this dose of MDMA, the concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was reduced by over 50% in hippocampus, cortex and striatum, reflecting neurotoxic damage. There was no change in the concentration of dopamine or 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. p-Chloroamphetamine (PCA), another compound which produces a neurotoxic loss of cerebral 5-HT content, when given at a dose of 5 mg kg−1 also significantly increased the formation of 2,3-DHBA (but not 2,5-DHBA) in the dialysate for over 4.5 h. post-injection starting 2 h after treatment. In contrast, fenfluramine administration (15 mg kg−1, i.p.) failed to increase the 2,3-DHBA or 2,5-DHBA concentration in the dialysate. A single fenfluramine injection nevertheless also markedly decreased the concentration of 5-HT and 5-HIAA in the hippocampus, cortex and striatum seven days later. When rats pretreated with fenfluramine (15 mg kg−1, i.p.) seven days earlier were given MDMA (15 mg kg−1, i.p.) no increase in 2,3-DHBA was seen in the dialysate from the hippocampal probe. This indicates that the increase in free radical formation following MDMA is occurring in 5-HT neurones which have been damaged by the prior fenfluramine injection. Administration of the free radical scavenging agent α-phenyl-N-tert-butyl nitrone (PBN; 120 mg kg−1, i.p.) 10 min before and 120 min after an MDMA (15 mg kg−1, i.p.) injection prevented the acute rise in the 2,3-DHBA concentration in the dialysate and attenuated by 30% the long term damage to hippocampal 5-HT neurones (as indicated by a smaller MDMA-induced decrease in both the concentration of 5-HT and 5-HIAA and also the binding of [3H]-paroxetine). These data indicate that a major mechanism by which MDMA and PCA induce damage to 5-hydroxytryptaminergic neurones in rat brain is by increasing the formation of free radicals. These probably result from the degradation of catechol and quinone metabolites of these substituted amphetamines. In contrast, fenfluramine induces damage by another mechanism not involving free radicals; a proposal supported by some of our earlier indirect studies. We suggest that these different modes of action render untenable the recent suggestion that MDMA will not be neurotoxic in humans because fenfluramine appears safe at clinical doses. PMID:9222545

Requirement of histidine 217 for ubiquinone reductase activity (Qi site) in the cytochrome bc1 complex.

PubMed

Gray, K A; Dutton, P L; Daldal, F

1994-01-25

Folding models suggest that the highly conserved histidine 217 of the cytochrome b subunit from the cytochrome bc1 complex is close to the quinone reductase (Qi) site. This histidine (bH217) in the cytochrome b polypeptide of the photosynthetic bacterium Rhodobacter capsulatus has been replaced with three other residues, aspartate (D), arginine (R), and leucine (L). bH217D and bH217R are able to grow photoheterotrophically and contain active cytochrome bc1 complexes (60% of wild-type activity), whereas the bH217L mutant is photosynthetically incompetent and contains a cytochrome bc1 complex that has only 10% of the wild-type activity. Single-turnover flash-activated electron transfer experiments show that cytochrome bH is reduced via the Qo site with near native rates in the mutant strains but that electron transfer between cytochrome bH and quinone bound at the Qi site is greatly slowed. These results are consistent with redox midpoint potential (Em) measurements of the cytochrome b subunit hemes and the Qi site quinone. The Em values of cyt bL and bH are approximately the same in the mutants and wild type, although the mutant strains have a larger relative concentration of what may be the high-potential form of cytochrome bH, called cytochrome b150. However, the redox properties of the semiquinone at the Qi site are altered significantly. The Qi site semiquinone stability constant of bH217R is 10 times higher than in the wild type, while in the other two strains (bH217D and bH217L) the stability constant is much lower than in the wild type. Thus H217 appears to have major effects on the redox properties of the quinone bound at the Qi site. These data are incorporated into a suggestion that H217 forms part of the binding pocket of the Qi site in a manner reminiscent of the interaction between quinone bound at the Qb site and H190 of the L subunit of the bacterial photosynthetic reaction center.

A novel o-aminophenol oxidase responsible for formation of the phenoxazinone chromophore of grixazone.

PubMed

Suzuki, Hirokazu; Furusho, Yasuhide; Higashi, Tatsuichiro; Ohnishi, Yasuo; Horinouchi, Sueharu

2006-01-13

Grixazone contains a phenoxazinone chromophore and is a secondary metabolite produced by Streptomyces griseus. In the grixazone biosynthesis gene cluster, griF (encoding a tyrosinase homolog) and griE (encoding a protein similar to copper chaperons for tyrosinases) are encoded. An expression study of GriE and GriF in Escherichia coli showed that GriE activated GriF by transferring copper ions to GriF, as has been observed for a Streptomyces melanogenesis system in which the MelC1 copper chaperon transfers copper ions to MelC2 tyrosinase. In contrast with tyrosinases, GriF showed no monophenolase activity, although it oxidized various o-aminophenols as preferable substrates rather than catechol-type substrates. Deletion of the griEF locus on the chromosome resulted in accumulation of 3-amino-4-hydroxybenzaldehyde (3,4-AHBAL) and its acetylated compound, 3-acetylamino-4-hydroxybenzaldehyde. GriF oxidized 3,4-AHBAL to yield an o-quinone imine derivative, which was then non-enzymatically coupled with another molecule of the o-quinone imine to form a phenoxazinone. The coexistence of N-acetylcysteine in the in vitro oxidation of 3,4-AH-BAL by GriF resulted in the formation of grixazone A, suggesting that the -SH group of N-acetylcysteine is conjugated to the o-quinone imine formed from 3,4-AHBAL and that the conjugate is presumably coupled with another molecule of the o-quinone imine. GriF is thus a novel o-aminophenol oxidase that is responsible for the formation of the phenoxazinone chromophore in the grixazone biosynthetic pathway.

Electron Shuttling by Dissolved Humic Substances: Using Fluorescence Spectroscopy to Move Beyond the Laboratory to Natural Lakes, Streams and Groundwaters

NASA Astrophysics Data System (ADS)

McKnight, D. M.

2017-12-01

Humic substances are an important class of reactive chemical species in natural waters, and one important role is their capacity to as an electron acceptor and/or electron shuttle to ferric iron present as solid phase ferric oxides. Several lines of evidence point to quinone-like moieties being the main redox active moieties that can be used by microbes in respiration. Concomitantly, the humic fraction of dissolved organic mater (DOM) contains the dominant fluorophores in many natural waters. Examination of excitation emission matrices (EEMs) across redox gradients in diverse aquatic systems show that the EEMs are generally red-shifted under reducing conditions, such as anoxic bottom waters in lakes and hypoxic waters in riparian wetlands. Furthermore, there is striking similarity between the humic fluorophores that are resolved by statistical analysis and the fluorescence spectra of model quinone compounds, with the more reduced species having red-shifted fluorescence spectra. This apparent red-shift can be quantified based on the distribution of apparently "quinone-like", "semi-quinone-like" and "hydroquinone-like" fluorophores determined by the PARAFAC statistical analysis. Because fluorescence spectroscopy can be applied at ambient DOM concentrations for samples that have been maintained in an anoxic condition, fluorescence spectroscopy can provide insight into the role of humic electron shuttling in natural systems. Examples are presented demosntrating the changing EEMs in anoxic bottomwaters in a lake in the McMurdo Dry Valleys following a major flood event and the role of organic material in the mobilization of arsenic in shallow groundwater in South East Asia.

Enhancement of DMNQ-induced hepatocyte toxicity by cytochrome P450 inhibition.

PubMed

Ishihara, Yasuhiro; Shiba, Dai; Shimamoto, Norio

2006-07-15

Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative stress via the redox cycle and the arylation of intracellular nucleophiles. As the redox cycle is catalyzed by NADPH cytochrome P450 reductase, cytochrome P450 systems are expected to be related to the cytotoxicity induced by redox-cycling quinones. Thus, we investigated the relationship between cytochrome P450 systems and quinone toxicity for rat primary hepatocytes using an arylator, 1,4-benzoquinone (BQ), and a redox cycler, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). The hepatocyte toxicity of both BQ and DMNQ increased in a time- and dose-dependent manner. Pretreatment with cytochrome P450 inhibitors, such as SKF-525A (SKF), ketoconazole and 2-methy-1,2-di-3-pyridyl-1-propanone, enhanced the hepatocyte toxicity induced by DMNQ but did not affect BQ-induced hepatocyte toxicity. The production of superoxide anion and the levels of glutathione disulfide and thiobarbituric-acid-reactive substances were increased by treatment with DMNQ, and SKF pretreatment further enhanced their increases. In addition, NADPH oxidation in microsomes was increased by treatment with DMNQ and further augmented by pretreatment with SKF, and a NADPH cytochrome P450 reductase inhibitor, diphenyleneiodonium chloride completely suppressed NADPH oxidations increased by treatment with either DMNQ- or DMNQ + SKF. Pretreatment with antioxidants, such as alpha-tocopherol, reduced glutathione, N-acetyl cysteine or an iron ion chelator deferoxamine, totally suppressed DMNQ- and DMNQ + SKF-induced hepatocyte toxicity. These results indicate that the hepatocyte toxicity of redox-cycling quinones is enhanced under cytochrome P450 inhibition, and that this enhancement is caused by the potentiation of oxidative stress.

Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein.

PubMed

da Silva, Fernanda Luna; Coelho Cerqueira, Eduardo; de Freitas, Mônica Santos; Gonçalves, Daniela Leão; Costa, Lilian Terezinha; Follmer, Cristian

2013-01-01

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro. Copyright © 2012 Elsevier Ltd. All rights reserved.

4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase.

PubMed

Garcia-Jimenez, Antonio; Teruel-Puche, Jose Antonio; Ortiz-Ruiz, Carmen Vanessa; Berna, Jose; Tudela, Jose; Garcia-Canovas, Francisco

2016-08-01

4-n-Butylresorcinol (BR) is considered the most potent inhibitor of tyrosinase, which is why it is used in cosmetics as a depigmenting agent. However, this work demonstrates that BR is a substrate of this enzyme. The Em (met-tyrosinase) form is not active on BR, but Eox (oxy-tyrosinase) can act on this molecule, hydroxylating it to o-diphenol. In turn, this is oxidized to an o-quinone, which isomerizes to a red p-quinone. Thus, for tyrosinase to act on this compound, a mechanism to generate Eox in the medium is required, which can be achieved by means of hydrogen peroxide or ascorbic acid. A kinetic analysis of the proposed mechanism allows its kinetic characterization: catalytic constant kcatBR (8.49 ± 0.20 s(-1) ) and Michaelis-constant KMBR (60.26 ± 8.76 μM). These findings are compared with those for other monophenolic substrates of tyrosinase. Studies of BR docking to the Em form of the enzyme show that the hydroxyl group in C-1 position is oriented toward the copper atom A (CuA), as in it is L-tyrosine. As regards Eox , BR is oriented with the carbon in C-6 position ready to be hydroxylated. The reaction of BR originates o-quinones, which isomerize to p-quinones, which in turn, could react with thiol compounds, a finding that could have important implications for pharmacology and the cosmetic industry. © 2016 IUBMB Life, 68(8):663-672, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of Leishmania infantum.

PubMed

Venkatesan, Santhosh Kannan; Shukla, Anil Kumar; Dubey, Vikash Kumar

2010-10-01

Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol-redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9-aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9-aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed. (c) 2010 Wiley Periodicals, Inc.

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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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.

The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions.

PubMed

Qu, Na; Li, Feng; Shao, Bo; Shao, Jie; Zhai, Guijin; Wang, Fuyi; Zhu, Ben-Zhan

2016-10-17

The phenolic hydroxyl group of tyrosine residue plays a crucial role in the structure and function of many proteins. However, little study has been reported about its modification by chemical agents under physiological conditions. In this study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid metabolites of polyhalogenated aromatic compounds. The modification was found to be mainly due to the formation of a variety of fluoroquinone-O-tyrosine conjugates and their hydroxylated derivatives via nucleophilic substitution pathway. Analogous modifications were observed for tyrosine-containing peptides. Further studies showed that the blockade of the reactive phenolic hydroxyl group of tyrosine in the substrate peptide, even by very low concentration of tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine phosphorylation. This is the first report showing the exceptionally facile chemical modification of the phenolic hydroxyl group of tyrosine by polyhalogenated quinones under normal physiological conditions, which may have potential biological and toxicological implications.

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.

Substituents on Quinone Methides Strongly Modulate Formation and Stability of Their Nucleophilic Adducts

PubMed Central

Weinert, Emily E.; Dondi, Ruggero; Colloredo-Melz, Stefano; Frankenfield, Kristen N.; Mitchell, Charles H.; Freccero, Mauro; Rokita, Steven E.

2008-01-01

Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 hr. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span five orders of magnitude with electron rich species reacting most slowly and electron deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application. PMID:16953635

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.

HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor.

PubMed

Kogan, Natalya M; Schlesinger, Michael; Priel, Esther; Rabinowitz, Ruth; Berenshtein, Eduard; Chevion, Mordechai; Mechoulam, Raphael

2007-01-01

Anthracyclines, a large group of quinonoid compounds, are used to treat some forms of cancer. Although highly effective in cancer therapy, the mechanism of action of these compounds is not specific; they act on cancer and other cells by numerous mechanisms. A new anticancer quinone (HU-331) was synthesized from cannabidiol. It shows significant high efficacy against human cancer cell lines in vitro and against in vivo tumor grafts in nude mice. In this study, we investigated its mode of action and present evidence on its unique mechanism. HU-331 does not cause cancer cell cycle arrest, cell apoptosis, or caspase activation. HU-331-caused cell death of human cancer cell lines is not mediated by reactive oxygen intermediates/species, as exposure to HU-331 failed to elicit the generation of reactive oxygen species. HU-331 inhibits DNA topoisomerase II even at nanomolar concentrations but has only a slight nonsignificant effect on DNA topoisomerase I action. The cannabinoid quinone HU-331 is a highly specific inhibitor of topoisomerase II, compared with most known anticancer quinones. It might represent a new potent anticancer drug.

Time-resolved fluorescence spectroscopic study of flavin fluorescence in purified enzymes of bioluminescent bacteria

NASA Astrophysics Data System (ADS)

Vetrova, Elena; Kudryasheva, N.; Cheng, K.

2006-10-01

Time-resolved fluorescence intensity and anisotropy decay measurements have been used to study the environment and rotational mobility of endogenous flavin in two purified enzymes of bioluminescent bacteria, Luciferase from Photobacterium leiognathi and NAD(P)H:FMN-oxidoreductase from Vibrio fischeri. We compared the time-resolved fluorescence parameters, intensity decay lifetimes, rotational correlation times, and their fractional contribution, of the endogeneous flavin fluorescence in each of the two enzymes in the presence or absence of quinones of different structures and redox potentials. The endogeneous flavin exhibited multi-exponential decay characteristics as compared to a single decay lifetime of around 5 ns for free flavin, suggesting a complex and heterogeneous environment of flavin bound to the enzyme. In addition, a significant increase in the rotational correlation time and a certain degree of ordering of the molecule were observed for endogenous flavin when compared to a single and fast rotational correlation time of 150 ps of free flavin. Quinone significantly altered both the lifetime and rotational characteristics of endogenous flavin suggesting specific interactions of quinones to the endogeneous flavin in the bacterial enzyme.

Ligninolytic basidiomycetes as promising organisms for the mycoremediation of PAH-contaminated Environments

NASA Astrophysics Data System (ADS)

Pozdnyakova, N. N.; Balandina, S. A.; Dubrovskaya, E. V.; Golubev, C. N.; Turkovskaya, O. V.

2018-01-01

Primary screening of ligninolytic fungi belonging to wood- and soil-inhabiting basidiomycetes revealed their ability to degrade three-ringed PAHs with formation of quinone metabolites at the first stage. The degradative activity was both species and strain specific, and some differences in the “chances” for the formed quinones were found. They were the main end metabolites in the degradation of PAHs by Stropharia rugosoannulata and Agaricus bisporus. During PAH degradation by strains of Trametes versicolor, Pleurotus ostreatus, Schizophyllum commune, and Bjerkandera adusta similar metabolites were detected during the cultivation, but they were utilized further. The results supported the hypothesis that the degree of PAH degradation may depend on the composition of the extracellular ligninolytic complex of the fungi: in the presence of a single ligninolytic enzyme, laccase, the accumulation of quinone metabolites takes place; their further utilization is possible with the participation of ligninolytic peroxidases. The data obtained showed the necessity not only to identify the metabolites formed, but also to study the activity of the basic ligninolytic enzymes. It is important for the correct selection of fungal strains for mycoremediation.

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

Syntheses, structural characterization, and basic properties of unsymmetrically substituted biphenoquinones

NASA Astrophysics Data System (ADS)

Fujii, Ryotaro; Sugiura, Ken-ichi

2018-03-01

Unsymmetrically substituted biphenoquinones, 3,5-dimethyl-3‧,5‧-diphenylbiphenoquinone and 3,5-di-tert-butyl-3‧,5‧-diphenylbiphenoquinone, were prepared by a mixed oxidative coupling reaction of the corresponding phenols with potassium permanganate in CHCl3. The properties of the quinones such as reduction potential and visible light absorption were measured and positively shifted reduction potentials and bathochromic shifts as a result of light absorption were found to be characteristic of the π-expanded quinones. We also carried out single-crystal diffraction study and uncovered a unique packing motif attributable to their unsymmetrical structures.

Biosynthesis of pyrroloquinoline quinone. 1. Identification of biosynthetic precursors using /sup 13/C labeling and NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.

Liquid Quinones for Solvent-Free Redox Flow Batteries.

PubMed

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

2017-11-01

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 LiBF 4 /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.

Humic-like Products Formation via the Reaction of Phenol with Nitrite in Ice Phase

NASA Astrophysics Data System (ADS)

Min, D. W.; Choi, W.

2017-12-01

Understanding the chemical nature of humic substances is very important but the origin of humic substances in nature is not well known. Therefore, elucidating the mechanisms leading to the generation of humic substances in nature is of great interests. It is believed that humic substances are produced from the transformation of natural organic matters, like lignin, by biological pathways. Recently, it has been reported that monomer molecules like quinones and sugars could be polymerized with amino compounds to form humic-like substances. This humification process is considered as a possible mechanism of humic substances production in the environment. In this work, we report the first observation on the formation of humic-like substances from the reaction between phenol and nitrite under a frozen state. In aqueous solution, nitrite slowly reacts with phenol, producing phenolic compounds like nitrophenol. Under frozen state, however, phenol reacted rapidly with nitrite and produced diverse organic compounds, like hydroquinone, dimerized phenolic substances, and much bigger molecules such as humic-like substances. The humic-like substances produced in ice are likely caused by the formation of phenolic radical and nitrosonium ion. This work may provide some insights into unknown pathways for the origin of humic substances especially in frozen environments.

Degradation of anthracene by laccase of Trametes versicolor in the presence of different mediator compounds.

PubMed

Johannes, C; Majcherczyk, A; Hüttermann, A

1996-10-01

Laccase of Trametes versicolor was generally able to oxidize anthracene in vitro. After 72 h incubation about 35% of the anthracene was transformed stoichiometrically to 9,10-anthraquinone. Transformation of anthracene increased rapidly in the presence of different mediators that readily generate stable radicals: 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 1-hydroxybenzotriazole. For the reaction, the presence of both the laccase and the mediator was necessary. In the presence of 0.005 mM 1-hydroxybenzotriazole this conversion had removed 47% of the anthracene after 72 h; 75% of the substrate was oxidized during this period when ABTS (1 mM) was used as mediator. In contrast to reactions without or with only low concentrations of a mediator, there was a discrepancy between the disappearance of anthracene and the formation of 9,10-anthraquinone in mediator-forced reactions. Coupling-products of mediators with anthracene degradation products were found. Anthracene disappeared nearly completely after incubation for 72 h with laccase in a 0.1 mM solution of 1-hydroxybenzotriazole and was transformed to 9,10-anthraquinone in about 80% yield; 90% of the substrate was transformed in the presence of ABTS (2.0 mM) resulting again in 80% quinone. Phenothiazine was not effective in this system.

Pulsed discharge plasma induced Fenton-like reactions for the enhancement of the degradation of 4-chlorophenol in water.

PubMed

Hao, Xiaolong; Zhou, Minghua; Xin, Qing; Lei, Lecheng

2007-02-01

To sufficiently utilize chemically active species and enhance the degradation rate and removal efficiency of toxic and biorefractory organic pollutant para-chlorophenol (para-CP), the introductions of iron metal ions (Fe2+/Fe3+) into either pulsed discharge plasma (PDP) process or the PDP process with TiO2 photo-catalyst were tentatively performed. The experimental results showed that under the same experimental condition, the degradation rate and removal efficiency of para-CP were greatly enhanced by the introduction of iron ions (Fe2+/Fe3+) into the PDP process. Moreover, when iron ions and TiO2 were added together in the PDP process, the degradation rate and removal energy of para-CP further improved. The possible mechanism was discussed that the obvious promoting effects were attributed to ferrous ions via plasma induced Fenton-like reactions by UV light irradiation excited and hydrogen peroxide formed in pulsed electrical discharge, resulting in a larger amount of hydroxyl radicals produced from the residual hydrogen peroxide. In addition, the regeneration of ferric ions to ferrous ions facilitates the progress of plasma induced Fenton-like reactions by photo-catalytic reduction of UV light, photo-catalytic reduction on TiO2 surface and electron transfer of quinone intermediates, i.e. 1,4-hydroquinone and 1,4-benzoquinone.

Platinum Nanoparticles: Efficient and Stable Catechol Oxidase Mimetics.

PubMed

Liu, Yi; Wu, Haohao; Chong, Yu; Wamer, Wayne G; Xia, Qingsu; Cai, Lining; Nie, Zhihong; Fu, Peter P; Yin, Jun-Jie

2015-09-09

Although enzyme-like nanomaterials have been extensively investigated over the past decade, most research has focused on the peroxidase-like, catalase-like, or SOD-like activity of these nanomaterials. Identifying nanomaterials having oxidase-like activities has received less attention. In this study, we demonstrate that platinum nanoparticles (Pt NPs) exhibit catechol oxidase-like activity, oxidizing polyphenols into the corresponding o-quinones. Four unique approaches are employed to demonstrate the catechol oxidase-like activity exerted by Pt NPs. First, UV-vis spectroscopy is used to monitor the oxidation of polyphenols catalyzed by Pt NPs. Second, the oxidized products of polyphenols are identified by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution mass spectrometry (HRMS) identification. Third, electron spin resonance (ESR) oximetry techniques are used to confirm the O2 consumption during the oxidation reaction. Fourth, the intermediate products of semiquinone radicals formed during the oxidation of polyphenols are determined by ESR using spin stabilization. These results indicate Pt NPs possess catechol oxidase-like activity. Because polyphenols and related bioactive substances have been explored as potent antioxidants that could be useful for the prevention of cancer and cardiovascular diseases, and Pt NPs have been widely used in the chemical industry and medical science, it is essential to understand the potential effects of Pt NPs for altering or influencing the antioxidant activity of polyphenols.

Advanced oxidation of benzene, toluene, ethylbenzene and xylene isomers (BTEX) by Trametes versicolor.

PubMed

Aranda, Elisabet; Marco-Urrea, Ernest; Caminal, Gloria; Arias, María E; García-Romera, Inmaculada; Guillén, Francisco

2010-09-15

Advanced oxidation of benzene, toluene, ethylbenzene, and o-, m-, and p-xylene (BTEX) by the extracellular hydroxyl radicals (*OH) generated by the white-rot fungus Trametes versicolor is for the first time demonstrated. The production of *OH was induced by incubating the fungus with 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe3+-EDTA. Under these conditions, *OH were generated through DBQ redox cycling catalyzed by quinone reductase and laccase. The capability of T. versicolor growing in malt extract medium to produce *OH by this mechanism was shown during primary and secondary metabolism, and was quantitatively modulated by the replacement of EDTA by oxalate and Mn2+ addition to DBQ incubations. Oxidation of BTEX was observed only under *OH induction conditions. *OH involvement was inferred from the high correlation observed between the rates at which they were produced under different DBQ redox cycling conditions and those of benzene removal, and the production of phenol as a typical hydroxylation product of *OH attack on benzene. All the BTEX compounds (500 microM) were oxidized at a similar rate, reaching an average of 71% degradation in 6 h samples. After this time oxidation stopped due to O2 depletion in the closed vials used in the incubations. Copyright 2010 Elsevier B.V. All rights reserved.

Anthocyanins encapsulated by PLGA@PEG nanoparticles potentially improved its free radical scavenging capabilities via p38/JNK pathway against Aβ1-42-induced oxidative stress.

PubMed

Amin, Faiz Ul; Shah, Shahid Ali; Badshah, Haroon; Khan, Mehtab; Kim, Myeong Ok

2017-02-07

In order to increase the bioavailability of hydrophilic unstable drugs like anthocyanins, we employed a polymer-based nanoparticles approach due to its unique properties such as high stability, improved bioavailability and high water-soluble drug loading efficiency. Anthocyanins constitute a subfamily of flavonoids that possess anti-oxidative, anti-inflammatory and neuroprotective properties. However, anthocyanins are unstable because their phenolic hydroxyl groups are easily oxidized into quinones, causing a reduced biological activity. To overcome this drawback and improve the free radical scavenging capabilities of anthocyanins, in the current study we for the first time encapsulated the anthocyanins in biodegradable nanoparticle formulation based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-2000. The biological activity and neuroprotective effect of anthocyanin loaded nanoparticles (An-NPs) were investigated in SH-SY5Y cell lines. Morphological examination under transmission electron microscopy (TEM) showed the formation of smooth spherically shaped nanoparticles. The average particle size and zeta potential of An-NPs were in the range of 120-165 nm and -12 mV respectively, with a low polydispersity index (0.4) and displayed a biphasic release profile in vitro. Anthocyanins encapsulation in PLGA@PEG nanoparticles (NPs) did not destroy its inherent properties and exhibit more potent neuroprotective properties. An-NPs were nontoxic to SH-SY5Y cells and increased their cell viability against Aβ 1-42 by its free radical scavenging characteristics and abrogated ROS generation via the p38-MAPK/JNK pathways accompanied by induction of endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Comparative to native bulk anthocyanins, An-NPs effectively attenuated Alzheimer's markers like APP (amyloid precursor protein), BACE-1 (beta-site amyloid precursor protein cleaving enzyme 1), neuroinflammatory markers such as p-NF-kB (phospho-nuclear factor kappa B), TNF-α (tumor necrosis factor) and iNOS (inducible nitric oxide synthase) and neuroapoptotic markers including Bax, Bcl 2 , and Caspase-3 protein expressions accompanied by neurodegeneration against Aβ 1-42 in SH-SY5Y cell lines. Overall, this data not only confirmed the therapeutic potential of anthocyanins in reducing AD pathology but also offer an effective way to improve the efficiency of anthocyanins through the use of nanodrug delivery systems.

Spectroscopic and molecular docking studies on the charge transfer complex of bovine serum albumin with quinone in aqueous medium and its influence on the ligand binding property of the protein.

PubMed

Satheshkumar, Angupillai; Elango, Kuppanagounder P

2014-09-15

The spectral techniques such as UV-Vis, (1)H NMR and fluorescence and electrochemical experiments have been employed to investigate the interaction between 2-methoxy-3,5,6-trichloro-1,4-benzoquinone (MQ; a water soluble quinone) and bovine serum albumin (BSA) in aqueous medium. The fluorescence of BSA was quenched by MQ via formation of a 1:1 BSA-MQ charge transfer adduct with a formation constant of 3.3×10(8) L mol(-1). Based on the Forster's theory the binding distance between them is calculated as 2.65 nm indicating high probability of binding. For the first time, influence of quinone on the binding property of various types of ligands such as aspirin, ascorbic acid, nicotinimide and sodium stearate has also been investigated. The results indicated that the strong and spontaneous binding existing between BSA and MQ, decreased the intensity of binding of these ligands with BSA. Since Tryptophan (Trp) is the basic residue present in BSA, a comparison between binding property of Trp-MQ adduct with that of BSA-MQ with these ligands has also been attempted. 1H NMR titration study indicated that the Trp forms a charge transfer complex with MQ, which reduces the interaction of Trp with the ligands. Molecular docking study supported the fact that the quinone interacts with the Trp212 unit of the BSA and the free energy change of binding (ΔG) for the BSA-MQ complex was found to be -46 kJ mol(-1), which is comparable to our experimental free energy of binding (-49 kJ mol(-1)) obtained from fluorescence study. Copyright © 2014 Elsevier B.V. All rights reserved.

Role of the NAD(P)H quinone oxidoreductase NQR and the cytochrome b AIR12 in controlling superoxide generation at the plasma membrane.

PubMed

Biniek, Catherine; Heyno, Eiri; Kruk, Jerzy; Sparla, Francesca; Trost, Paolo; Krieger-Liszkay, Anja

2017-04-01

The quinone reductase NQR and the b-type cytochrome AIR12 of the plasma membrane are important for the control of reactive oxygen species in the apoplast. AIR12 and NQR are two proteins attached to the plant plasma membrane which may be important for generating and controlling levels of reactive oxygen species in the apoplast. AIR12 (Auxin Induced in Root culture) is a single gene of Arabidopsis that codes for a mono-heme cytochrome b. The NADPH quinone oxidoreductase NQR is a two-electron-transferring flavoenzyme that contributes to the generation of O 2 •- in isolated plasma membranes. A. thaliana double knockout plants of both NQR and AIR12 generated more O 2 •- and germinated faster than the single mutant affected in AIR12. To test whether NQR and AIR12 are able to interact functionally, recombinant purified proteins were added to plasma membranes isolated from soybean hypocotyls. In vitro NADH-dependent O 2 •- production at the plasma membrane in the presence of NQR was reduced upon addition of AIR12. Electron donation from semi-reduced menadione to AIR12 was shown to take place. Biochemical analysis showed that purified plasma membrane from soybean hypocotyls or roots contained phylloquinone and menaquinone-4 as redox carriers. This is the first report on the occurrence of menaquinone-4 in eukaryotic photosynthetic organisms. We propose that NQR and AIR12 interact via the quinone, allowing an electron transfer from cytosolic NAD(P)H to apoplastic monodehydroascorbate and control thereby the level of reactive oxygen production and the redox state of the apoplast.

Light-adaptation of photosystem II is mediated by the plastoquinone pool.

PubMed

Ahrling, Karin A; Peterson, Sindra

2003-07-01

During the first few enzymatic turnovers after dark-adaptation of photosystem II (PSII), the relaxation rate of the EPR signals from the Mn cluster and Y(D)(*) are significantly enhanced. This light-adaptation process has been suggested to involve the appearance of a new paramagnet on the PSII donor side [Peterson, S., Ahrling, K., Högblom, J., and Styring, S. (2003) Biochemistry 42, 2748-2758]. In the present study, a correlation is established between the observed relaxation enhancement and the redox state of the quinone pool. It is shown that the addition of quinol to dark-adapted PSII membrane fragments induces relaxation enhancement already after a single oxidation of the Mn, comparable to that observed after five oxidations in samples with quinones (PPBQ or DQ) added. The saturation behavior of Y(D)(*) revealed that with quinol added in the dark, a single flash was necessary for the relaxation enhancement to occur. The quinol-induced relaxation enhancement of PSII was also activated by illumination at 200 K. Whole thylakoids, with no artificial electron acceptor present but with an intact plastoquinone pool, displayed the same relaxation enhancement on the fifth flash as membrane fragments with exogenous quinones present. We conclude that (i) reduction of the quinone pool induces the relaxation enhancement of the PSII donor-side paramagnets, (ii) light is required for the quinol to effect the relaxation enhancement, and (iii) light-adaptation occurs in the intact thylakoid system, when the endogenous plastoquinone pool is gradually reduced by PSII turnover. It seems clear that a species on the PSII donor side is reduced by the quinol, to become a potent paramagnetic relaxer. On the basis of XANES reports, we suggest that this species may be the Mn ions not involved in the cyclic redox changes of the oxygen-evolving complex.

Ultrafast Electron Transfer Kinetics in the LM Dimer of Bacterial Photosynthetic Reaction Center from Rhodobacter sphaeroides.

PubMed

Sun, Chang; Carey, Anne-Marie; Gao, Bing-Rong; Wraight, Colin A; Woodbury, Neal W; Lin, Su

2016-06-23

It has become increasingly clear that dynamics plays a major role in the function of many protein systems. One system that has proven particularly facile for studying the effects of dynamics on protein-mediated chemistry is the bacterial photosynthetic reaction center from Rhodobacter sphaeroides. Previous experimental and computational analysis have suggested that the dynamics of the protein matrix surrounding the primary quinone acceptor, QA, may be particularly important in electron transfer involving this cofactor. One can substantially increase the flexibility of this region by removing one of the reaction center subunits, the H-subunit. Even with this large change in structure, photoinduced electron transfer to the quinone still takes place. To evaluate the effect of H-subunit removal on electron transfer to QA, we have compared the kinetics of electron transfer and associated spectral evolution for the LM dimer with that of the intact reaction center complex on picosecond to millisecond time scales. The transient absorption spectra associated with all measured electron transfer reactions are similar, with the exception of a broadening in the QX transition and a blue-shift in the QY transition bands of the special pair of bacteriochlorophylls (P) in the LM dimer. The kinetics of the electron transfer reactions not involving quinones are unaffected. There is, however, a 4-fold decrease in the electron transfer rate from the reduced bacteriopheophytin to QA in the LM dimer compared to the intact reaction center and a similar decrease in the recombination rate of the resulting charge-separated state (P(+)QA(-)). These results are consistent with the concept that the removal of the H-subunit results in increased flexibility in the region around the quinone and an associated shift in the reorganization energy associated with charge separation and recombination.

Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

PubMed

Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

2013-01-01

Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

Enhancement of Anti-Inflammatory Activity of Aloe vera Adventitious Root Extracts through the Alteration of Primary and Secondary Metabolites via Salicylic Acid Elicitation

PubMed Central

Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

2013-01-01

Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10–11 and 5–13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment. PMID:24358188

Partitioning of electron flux between the respiratory chains of the yeast Candida parapsilosis: parallel working of the two chains.

PubMed

Guerin, M G; Camougrand, N M

1994-02-08

Partitioning of the electron flux between the classical and the alternative respiratory chains of the yeast Candida parapsilosis, was measured as a function of the oxidation rate and of the Q-pool redox poise. At low respiration rate, electrons from external NADH travelled preferentially through the alternative pathway as indicated by the antimycin A-insensitivity of electron flow. Inhibition of the alternative pathway by SHAM restored full antimycin A-sensitivity to the remaining electro flow. The dependence of the respiratory rate on the redox poise of the quinone pool was investigated when the electron flux was mediated either by the main respiratory chain (growth in the absence of antimycin A) or by the second respiratory chain (growth in the presence of antimycin A). In the former case, a linear relationship was found between these two parameters. In contrast, in the latter case, the relationship between Q-pool reduction level and electron flux was non-linear, but it could be resolved into two distinct curves. This second quinone is not reducible in the presence of antimycin A but only in the presence of high concentrations of myxothiazol or cyanide. Since two quinone species exist in C. parapsilosis, UQ9 and Qx (C33H54O4), we hypothesized that these two curves could correspond to the functioning of the second quinone engaged during the alternative pathway activity. Partitioning of electrons between both respiratory chains could occur upstream of complex III with the second chain functioning in parallel to the main one, and with the additional possibility of merging into the main one at the complex IV level.

Spectroscopic and molecular docking studies on the charge transfer complex of bovine serum albumin with quinone in aqueous medium and its influence on the ligand binding property of the protein

NASA Astrophysics Data System (ADS)

Satheshkumar, Angupillai; Elango, Kuppanagounder P.

2014-09-01

The spectral techniques such as UV-Vis, 1H NMR and fluorescence and electrochemical experiments have been employed to investigate the interaction between 2-methoxy-3,5,6-trichloro-1,4-benzoquinone (MQ; a water soluble quinone) and bovine serum albumin (BSA) in aqueous medium. The fluorescence of BSA was quenched by MQ via formation of a 1:1 BSA-MQ charge transfer adduct with a formation constant of 3.3 × 108 L mol-1. Based on the Forster’s theory the binding distance between them is calculated as 2.65 nm indicating high probability of binding. For the first time, influence of quinone on the binding property of various types of ligands such as aspirin, ascorbic acid, nicotinimide and sodium stearate has also been investigated. The results indicated that the strong and spontaneous binding existing between BSA and MQ, decreased the intensity of binding of these ligands with BSA. Since Tryptophan (Trp) is the basic residue present in BSA, a comparison between binding property of Trp-MQ adduct with that of BSA-MQ with these ligands has also been attempted. 1H NMR titration study indicated that the Trp forms a charge transfer complex with MQ, which reduces the interaction of Trp with the ligands. Molecular docking study supported the fact that the quinone interacts with the Trp212 unit of the BSA and the free energy change of binding (ΔG) for the BSA-MQ complex was found to be -46 kJ mol-1, which is comparable to our experimental free energy of binding (-49 kJ mol-1) obtained from fluorescence study.

Mechanistic study of photo-oxidation of Bisphenol-A (BPA) with hydrogen peroxide (H2O2) and sodium persulfate (SPS).

PubMed

Sharma, Jyoti; Mishra, I M; Kumar, Vineet

2016-01-15

The removal of Bisphenol-A (BPA) from contaminated water using advanced oxidation methods such as UV-C assisted oxidation by hydrogen peroxide (H2O2) and sodium persulfate (SPS) has been reported by the authors earlier (Sharma et al., 2015a). In the present study, the authors report the removal of BPA from aqueous solution by the above two methods and its degradation mechanism. UV-C light (254 nm wavelength, 40 W power) was applied to BPA contaminated water at natural pH (pHN) under room temperature conditions. Experiments were carried out with the initial BPA concentration in the range of 0.04 mM-0.31 mM and the oxidant/BPA molar ratio in the range of 294:1-38:1 for UV-C/H2O2 and 31.5-4.06:1 for UV-C/SPS systems. The removal of BPA enhanced with decreasing BPA concentration. The total organic carbon also decreased with the UV-C irradiation time under optimum conditions ([H2O2]0 = 11.76 mM; [SPS]0 = 1.26 mM; temperature (29 ± 3 °C). Competition of BPA for reaction with HO or [Formula: see text] radicals at its higher concentrations results in a decrease in the removal of BPA. The intermediates with smaller and higher molecular weights than that of BPA were found in the treated water. Based on GC-MS and FTIR spectra of the reaction mixture, the formation of hydroxylated by-products testified the HO mediated oxidation pathway in the BPA degradation, while the formation of quinones and phenoxy phenols pointed to the [Formula: see text] dominating pathway through the formation of hydroxycyclohexadienyl (HCHD) and BPA phenoxyl radicals. The main route of BPA degradation is the hydroxylation followed by dehydration, coupling and ring opening reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Significant role of UV and carbonate radical on the degradation of oxytetracycline in UV-AOPs: Kinetics and mechanism.

PubMed

Liu, Yiqing; He, Xuexiang; Duan, Xiaodi; Fu, Yongsheng; Fatta-Kassinos, Despo; Dionysiou, Dionysios D

2016-05-15

Carbonate radical (CO3(•-)), a selective oxidant, reacts readily with electron-rich compounds through electron transfer and/or hydrogen abstraction. In this study, the role of CO3(•-) in degrading oxytetracycline (OTC) by UV only, UV/H2O2 and UV/persulfate (UV/PS) advanced oxidation processes (AOPs) in the presence of HCO3(-) or CO3(2-) was investigated. For UV only process, the presence of photosensitizers, i.e., nitrate (NO3(-)) and natural organic matter (NOM), had different impacts on OTC degradation, i.e., an enhancing effect by NO3(-) due to the generation of HO(•) and a slight inhibiting effect by NOM possibly due to a light scattering effect. Differently for UV/H2O2 and UV/PS processes, the presence of NO3(-) hardly influenced the destruction of OTC. Generation of CO3(•-) presented a positive role on OTC degradation by UV/NO3(-)/HCO3(-). Such influence was also observed in the two studied AOPs in the presence of both bicarbonate and other natural water constituents. When various natural water samples from different sources were used as reaction matrices, UV only and UV/H2O2 showed an inhibiting effect while UV/PS demonstrated a comparable or even promoting effect in OTC decomposition. After elucidating the potential contribution of UV direct photolysis via excited state OTC* at an elevated reaction pH condition, putative OTC transformation byproducts via CO3(•-) reaction were identified by ultra-high definition accurate-mass quadrupole time-of-flight tandem mass spectrometry (QTOF/MS). Five different reaction pathways were subsequently proposed, including hydroxylation (+16 Da), quinonization (+14 Da), demethylation (-14 Da), decarbonylation (-28 Da) and dehydration (-18 Da). The significant role of UV at high pH and CO3(•-) on OTC removal from contaminated water was therefore demonstrated both kinetically and mechanistically. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phytochemical screening and free radical scavenging activity of Citrullus colocynthis seeds extracts

PubMed Central

Benariba, Nabila; Djaziri, Rabeh; Bellakhdar, Wafaa; Belkacem, Nacera; Kadiata, Marcel; Malaisse, Willy J.; Sener, Abdullah

2013-01-01

Objective To study the phytochemical screening of different extracts from Citrullus colocynthis (C. colocynthis ) seeds extracts and to assess their antioxidant activity on the DPPH free radical scavenging. Methods Phytochemical screening, total content of polyphenols and flavonoids of C. colocynthis seeds extracts, including a crude aqueous extract (E1), a defatted aqueous extract (E2), a hydromethanolic extract (HM), an ethyl acetate extract (EA) and a n-butanol extract (n-B) was carried out according to the standard methods and to assess their corresponding effect on the antioxidant activity of this plant. Results None of these extracts contained detectable amount of alkaloid, quinone, antraquinone, or reducing sugar. Catechic tannins and flavonoids were abundant in E1, HM and EA, whilst terpenoids were abundantly present in E1 and n-B but only weekly in HM. Coumarins were found in E2, EA and n-B. Polyphenols, expressed as gallic acid equivalent, amounted, per 100 g plant matter, to 329, 1002 and 150 mg in EA, HM an E1 respectively. Flavonoids, expressed as catechin equivalent, amounted, per 100 g plant matter to 620, 241 and 94 mg in EA, HM and E1 respectively. Comparable values were found in n-B and E1, with lower values in E2. Quercetin, myricetin and gallic acid were found in the EA and HM extracts by thin layer chromatography, The antioxidative effect of these extracts yielded, when tested at a concentration of 2 000 µg/mL in a 1,1-diphenyl-2-picrylhydrazyl assay, a reducing percentage of 88.8% with EA, 74.5% with HM and 66.2% with E1, and corresponding IC50 of 350, 580 and 500 µg/mL as compared to 1.1 µg/mL for ascorbic acid. Conclusions These qualitative and quantitative analytical data document the presence in C. colocynthis extracts of such chemical compounds as flavonoids responsible for the antioxidant activity, as well as other biological activities of this plant. PMID:23570014

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.

Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates.

PubMed

González-Pelayo, Silvia; López, Enol; Borge, Javier; de-Los-Santos-Álvarez, Noemí; López, Luis A

2018-06-01

The reaction of para -hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl₃ provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the desired products in synthetically useful yields. Evidence of involvement of a para -quinone methide intermediate in this coupling process was also provided. Preliminary biological evaluation demonstrated that some of the ferrocene derivatives available by this methodology exhibit significant cytotoxicity against several cancer cell lines with IC 50 values within the range of 1.07⁻4.89 μM.

The succession of microbial community in the organic rich fish-farm sediment during bioremediation by introducing artificially mass-cultured colonies of a small polychaete, Capitella sp. I.

PubMed

Kunihiro, Tadao; Miyazaki, Tomoaki; Uramoto, Yuuta; Kinoshita, Kyoko; Inoue, Akihiro; Tamaki, Sayaka; Hama, Daigo; Tsutsumi, Hiroaki; Ohwada, Kouichi

2008-01-01

We monitored seasonal changes of the abundance and composition of microorganisms in the fish-farm sediment in Kusuura Bay, Amakusa, Japan, using the quinone profiling technique, during bioremediation by introducing cultured colonies of polychaete, Capitella sp. I. In November 2004, approximately 9.2 million cultured worms were transferred to the fish-farm sediment, which increased rapidly, and reached 458.5 gWW/m(2) (528,000 indiv./m(2)) in March 2005. During this fast-increasing period of Capitella, the microbial quinone content of the surface sediment (0-2 cm) also increased markedly, and reached 237 micromol/m(2) in January 2005, although the water temperature decreased to the lowest levels in the year. Particularly, the mole fraction of ubiquinone-10 in total quinones in the sediment, indicating the presence of alpha subclass of Proteobacteria, increased by 9.3%. These facts suggest that the bacterial growth was enhanced markedly by the biological activities of worms in the sediment, and the bacteria played an important role in the decomposition of the organic matter in the sediment.

The 2-Methoxy Group Orientation Regulates the Redox Potential Difference between the Primary (QA) and Secondary (QB) Quinones of Type II Bacterial Photosynthetic Reaction Centers.

PubMed

de Almeida, Wagner B; Taguchi, Alexander T; Dikanov, Sergei A; Wraight, Colin A; O'Malley, Patrick J

2014-08-07

Recent studies have shown that only quinones with a 2-methoxy group can act simultaneously as the primary (Q A ) and secondary (Q B ) electron acceptors in photosynthetic reaction centers from purple bacteria such as Rb. sphaeroides . 13 C HYSCORE measurements of the 2-methoxy group in the semiquinone states, SQ A and SQ B , were compared with DFT calculations of the 13 C hyperfine couplings as a function of the 2-methoxy dihedral angle. X-ray structure comparisons support 2-methoxy dihedral angle assignments corresponding to a redox potential gap (Δ E m ) between Q A and Q B of 175-193 mV. A model having a methyl group substituted for the 2-methoxy group exhibits no electron affinity difference. This is consistent with the failure of a 2-methyl ubiquinone analogue to function as Q B in mutant reaction centers with a Δ E m of ∼160-195 mV. The conclusion reached is that the 2-methoxy group is the principal determinant of electron transfer from Q A to Q B in type II photosynthetic reaction centers with ubiquinone serving as both acceptor quinones.

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.

Chloroquine Binding Reveals Flavin Redox Switch Function of Quinone Reductase 2*

PubMed Central

Leung, Kevin K. K.; Shilton, Brian H.

2013-01-01

Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimalarial drugs, primaquine (PQ) and chloroquine (CQ). The structural differences between oxidized and reduced NQO2 and the structural basis for inhibition by PQ and CQ were investigated by x-ray crystallography. Structures of oxidized NQO2 in complex with PQ and CQ were solved at 1.4 Å resolution. CQ binds preferentially to reduced NQO2, and upon reduction of NQO2-CQ crystals, the space group changed from P212121 to P21, with 1-Å decreases in all three unit cell dimensions. The change in crystal packing originated in the negative charge and 4–5º bend in the reduced isoalloxazine ring of FAD, which resulted in a new mode of CQ binding and closure of a flexible loop (Phe126–Leu136) over the active site. This first structure of a reduced quinone reductase shows that reduction of the FAD cofactor and binding of a specific inhibitor lead to global changes in NQO2 structure and is consistent with a functional role for NQO2 as a flavin redox switch. PMID:23471972

Characterization of the ambient air content of parent polycyclic aromatic hydrocarbons in the Fort McKay region (Canada).

PubMed

Wnorowski, Andrzej

2017-05-01

This study presents the characterization of the gas-particle partition and size distribution of seven parent polycyclic aromatic hydrocarbons (PAHs) in ambient air samples collected in the proximity of oil sands exploration and compares their time-integrated concentration levels with nineteen analogous oxidation products - quinones. Gas-phase (GP) and particle-phase (PM) ambient air aerosol samples that were collected separately in summer for either 24 h or 12 h (day and night) revealed a higher PAH partition in the GP than in the PM, with the distribution over tenfold higher for light over heavy PAHs. Diurnal/nocturnal samples demonstrated that night conditions lead to lower concentrations, linking some of the sources of these compounds with daytime activity emissions. PAHs were observed to transform more efficiently in the GP, and quinone levels increased in the PM with time. Correlation data indicated that parent PAHs originated from primary emission sources associated with oil sand activities and that quinone formation paralleled a reduction in PAH levels. The findings of this study shed new light on characterization of PAHs in the Athabasca oil sands region. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Identifying the Tautomeric Form of a Deoxyguanosine-Estrogen Quinone Intermediate.

PubMed

Stack, Douglas E

2015-09-10

Mechanistic insights into the reaction of an estrogen o-quinone with deoxyguanosine has been further investigated using high level density functional calculations in addition to the use of 4-hyroxycatecholestrone (4-OHE₁) regioselectivity labeled with deuterium at the C1-position. Calculations using the M06-2X functional with large basis sets indicate the tautomeric form of an estrogen-DNA adduct present when glycosidic bonds cleavage occurs is comprised of an aromatic A ring structure. This tautomeric form was further verified by use of deuterium labelling of the catechol precursor use to form the estrogen o-quinone. Regioselective deuterium labelling at the C1-position of the estrogen A ring allows discrimination between two tautomeric forms of a reaction intermediate either of which could be present during glycosidic bond cleavage. HPLC-MS analysis indicates a reactive intermediate with a m/z of 552.22 consistent with a tautomeric form containing no deuterium. This intermediate is consistent with a reaction mechanism that involves: (1) proton assisted Michael addition; (2) re-aromatization of the estrogen A ring; and (3) glycosidic bond cleavage to form the known estrogen-DNA adduct, 4-OHE₁-1-N7Gua.

In vitro evidence for the formation of reactive intermediates of resveratrol in human liver microsomes.

PubMed

Steenwyk, R C; Tan, B

2010-01-01

Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound found in a variety of foods and over-the-counter health products. It has gained wide public use due to its potential health properties, and is available over-the-counter at health product stores. Although the safety profile of resveratrol has been minimally investigated in humans, resveratrol has been associated with observations of toxicity in vitro, and has been identified as a mechanism-based inhibitor of cytochrome P450 3A4. In addition, resveratrol has been rationally hypothesized to form reactive quinone methide metabolites, despite experimental evidence supporting this assumption. This work evaluates the potential for resveratrol to form glutathione-trapped reactive intermediates in human liver microsomes utilizing liquid chromatography and electrospray tandem mass spectrometry, and has resulted in the identification of several in vitro products including two hydroxylated metabolites (piceatannol and metabolite 2), and two pairs of regioisomeric glutathione adducts. The parallel metabolism of resveratrol to piceatannol and metabolite 2 (a putative quinone methide) are demonstrated to result in the formation of two putative quinone methide intermediates resulting in divergent mechanisms for formation of each pair of regioisomeric glutathione adducts.

The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding sites for water- and lipid-soluble substrates.

PubMed

Iwata, Momi; Lee, Yang; Yamashita, Tetsuo; Yagi, Takao; Iwata, So; Cameron, Alexander D; Maher, Megan J

2012-09-18

Bioenergy is efficiently produced in the mitochondria by the respiratory system consisting of complexes I-V. In various organisms, complex I can be replaced by the alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes the transfer of an electron from NADH via FAD to quinone, without proton pumping. The Ndi1 protein from Saccharomyces cerevisiae is a monotopic membrane protein, directed to the matrix. A number of studies have investigated the potential use of Ndi1 as a therapeutic agent against complex I disorders, and the NDH-2 enzymes have emerged as potential therapeutic targets for treatments against the causative agents of malaria and tuberculosis. Here we present the crystal structures of Ndi1 in its substrate-free, NAD(+)- and ubiquinone- (UQ2) complexed states. The structures reveal that Ndi1 is a peripheral membrane protein forming an intimate dimer, in which packing of the monomeric units within the dimer creates an amphiphilic membrane-anchor domain structure. Crucially, the structures of the Ndi1-NAD(+) and Ndi1-UQ2 complexes show overlapping binding sites for the NAD(+) and quinone substrates.

Possible roles of two quinone molecules in direct and indirect proton pumps of bovine heart NADH-quinone oxidoreductase (complex I).

PubMed

Ohnishi, S Tsuyoshi; Salerno, John C; Ohnishi, Tomoko

2010-12-01

In many energy transducing systems which couple electron and proton transport, for example, bacterial photosynthetic reaction center, cytochrome bc(1)-complex (complex III) and E. coli quinol oxidase (cytochrome bo(3) complex), two protein-associated quinone molecules are known to work together. T. Ohnishi and her collaborators reported that two distinct semiquinone species also play important roles in NADH-ubiquinone oxidoreductase (complex I). They were called SQ(Nf) (fast relaxing semiquinone) and SQ(Ns) (slow relaxing semiquinone). It was proposed that Q(Nf) serves as a "direct" proton carrier in the semiquinone-gated proton pump (Ohnishi and Salerno, FEBS Letters 579 (2005) 4555), while Q(Ns) works as a converter between one-electron and two-electron transport processes. This communication presents a revised hypothesis in which Q(Nf) plays a role in a "direct" redox-driven proton pump, while Q(Ns) triggers an "indirect" conformation-driven proton pump. Q(Nf) and Q(Ns) together serve as (1e(-)/2e(-)) converter, for the transfer of reducing equivalent to the Q-pool. Copyright © 2010 Elsevier B.V. All rights reserved.

Enhanced oxidation of flavan-3-ols and proanthocyanidin accumulation in water-stressed tea plants.

PubMed

Hernández, Iker; Alegre, Leonor; Munné-Bosch, Sergi

2006-06-01

(-)-Epicatechin (EC) and (-)-epigallocatechin gallate (EGCG), two major tea flavan-3-ols, have received attention in food science and biomedicine because of their potent antioxidant properties. In plants, flavan-3-ols serve as proanthocyanidin (PA) building blocks, and although both monomeric flavan-3-ols and PAs show antioxidant activity in vitro, their antioxidant function in vivo remains unclear. In the present study, EC quinone (ECQ) and EGCG quinone (EGCGQ), the oxidation products of EC and EGCG, increased up to 100- and 30-fold, respectively, in tea plants exposed to 19 days of water deficit. Oxidation of EC and EGCG preceded PAs accumulation in leaves, which increased from 35 to 53 mg gDW(-1) after 26 days of water deficit. Aside from the role monomeric flavan-3-ols may play in PAs biosynthesis, formation of ECQ and EGCGQ strongly negatively correlated with the extent of lipid peroxidation in leaves, thus supporting a protective role for these compounds in drought-stressed plants. Besides demonstrating flavonoid accumulation in drought-stressed tea plants, we show for the first time that EC and EGCG are oxidized to their respective quinones in plants in vivo.

Removal of p-alkylphenols from aqueous solutions by combined use of mushroom tyrosinase and chitosan beads.

PubMed

Yamada, Kazunori; Inoue, Tomoaki; Akiba, Yuji; Kashiwada, Ayumi; Matsuda, Kiyomi; Hirata, Mitsuo

2006-10-01

Enzymatic removal of p-alkylphenols from aqueous solutions was investigated through the two-step approach, the quinone conversion of p-alkylphenols with mushroom tyrosinase (EC 1.14.18.1) and the subsequent adsorption of quinone derivatives enzymatically generated on chitosan beads at pH 7.0 and 45 degrees C as the optimum conditions. This technique is quite effective for removal of various p-alkylphenols from an aqueous solution. The % removal values of 97-100% were obtained for p-n-alkylphenols with carbon chain lengths of 5 to 9. In addition, removal of other p-alkylphenols was enhanced by increasing either the tyrosinase concentration or the amount of added chitosan beads, and their % removal values reached >93 except for 4-tert-pentylphenol. This technique was also applicable to remove 4-n-octylphenol (4NOP) and 4-n-nonylphenol (4NNP) as suspected endocrine disrupting chemicals. The reaction of quinone derivatives enzymatically generated with the chitosan's amino groups was confirmed by the appearance of peaks for UV-visible spectrum measurements of the chitosan films incubated in the p-alkylphenol and tyrosinase mixture solutions. In addition, 4-tert-pentylphenol underwent tyrosinase-catalyzed oxidation in the presence of hydrogen peroxide.

Reaction of Hydroquinone with Hematite I. Study of Adsorption by Electrochemical-Scanning Tunneling Microscopy and X-ray Photoelectron Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stack, Andrew G; Eggleston, Carrick M; Engelhard, Mark H

2004-06-15

The reaction of hematite with quinones and the quinone moieties of larger molecules may be an important factor in limiting the rate ofreductive dissolution, especially by iron-reducing bacteria. Here, the electrochemical and physical properties of hydroquinone adsorbed on hematite surfaces at pH 2.5–3 were investigated with cyclic voltammetry (CV), electrochemical-scanning tunneling microscopy (EC-STM), and X-ray photoelectron spectroscopy (XPS). An oxidation peak for hydroquinone was observed in the CV experiments, as well as (photo)reduction of iron and decomposition of the solvent. The EC-STM results indicate that hydroquinone sometimes forms an ordered monolayer with ~1.1 H₂/nm², but can be fairly disordered (especiallymore » when viewed at larger scales). XPS results indicate that hydroquinone and benzoquinone are retained at the interface in increasing amounts as the reaction proceeds, but reduced iron is not observed. These results suggest that quinones do not adsorb by an inner-sphere complex where adsorbate–surface interactions determine the adsorbate surface structure, but rather in an outer-sphere complex where interactions among the adsorbate molecules dominate.« less

Reaction of hydroquinone with hematite I. Study of asdsorption by electrochemical-scanning tunneling microscopy and X-ray photoelectron spectroscopy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stack, Andrew G; Eggleston, Carrick M; Engelhard, Mark H

2003-12-01

The reaction of hematite with quinones and the quinone moieties of larger molecules may be an important factor in limiting the rate of reductive dissolution, especially by iron-reducing bacteria. Here, the electrochemical and physical properties of hydroquinone adsorbed on hematite surfaces at pH 2.5-3 were investigated with cyclic voltammetry (CV), electrochemical-scanning tunneling microscopy (EC-STM), and X-ray photoelectron spectroscopy (XPS). An oxidation peak for hydroquinone was observed in the CV experiments, as well as (photo)reduction of iron and decomposition of the solvent. The EC-STM results indicate that hydroquinone sometimes forms an ordered monolayer with {approx}1.1 QH{sub 2}/nm{sup 2}, but can bemore » fairly disordered (especially when viewed at larger scales). XPS results indicate that hydroquinone and benzoquinone are retained at the interface in increasing amounts as the reaction proceeds, but reduced iron is not observed. These results suggest that quinones do not adsorb by an inner-sphere complex where adsorbate-surface interactions determine the adsorbate surface structure, but rather in an outer-sphere complex where interactions among the adsorbate molecules dominate.« less

β-carboline derivatives and diphenols from soy sauce are in vitro quinone reductase (QR) inducers.

PubMed

Li, Ying; Zhao, Mouming; Parkin, Kirk L

2011-03-23

A murine hepatoma (Hepa 1c1c7) cellular bioassay was used to guide the isolation of phase II enzyme inducers from fermented soy sauce, using quinone reductase (QR) as a biomarker. A crude ethyl acetate extract, accounting for 8.7% of nonsalt soluble solids of soy sauce, was found to double relative QR specific activity at 25 μg/mL (concentration required to double was defined as a "CD value"). Further silica gel column fractionation yielded 17 fractions, 16 of which exhibited CD values for QR induction of <100 μg/mL. The four most potent fractions were subfractionated by column and preparative thin layer chromatography, leading to the isolation and identification of two phenolic compounds (catechol and daidzein) and two β-carbolines (flazin and perlolyrin), with respective CD values of 8, 35, 42, and 2 μM. Western blots confirmed that the increases in QR activity corresponded to dose-dependent increases in cellular levels of NAD[P]H:quinone oxidoreductase 1 protein by these four QR inducers. To the authors' knowledge, this is the first report on the ability of β-carboline-derived alkaloids to induce phase II enzymes.

Quantitative structure toxicity relationships for phenols in isolated rat hepatocytes.

PubMed

Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

2003-05-06

Quantitative structure toxicity relationship (QSTR) equations were obtained to predict and describe the cytotoxicity of 31 phenols using logLD(50) as a concentration to induce 50% cytotoxicity of isolated rat hepatocytes in 2 h and logP as octanol/water partitioning: logLD(50) (microM)=-0.588(+/-0.059)logP+4.652(+/-0.153) (n=27, r(2)=0.801, s=0.261, P<1 x 10(-9)). Hydroquinone, catechol, 4-nitrophenol, and 2,4-dinitrophenol were outliers for this equation. When the ionization constant pK(a) was considered as a contributing factor a two-parameter QSTR equation was derived: logLD(50) (microM)=-0.595(+/-0.051)logP+0.197(+/-0.029)pK(a)+2.665(+/-0.281) (n=28, r(2)=0.859, s=0.218, P<1 x 10(-6)). Using sigma+, the Brown variation of the Hammet electronic constant, as a contributing parameter, the cytotoxicity of phenols towards hepatocytes were defined by logLD(50) (microM)=-0.594(+/-0.052)logP-0.552(+/-0.085)sigma+ +4.540(+/-0.132) (n=28, r(2)=0.853, s=0.223, P<1 x 10(-6)). Replacing sigma+ with the homolytic bond dissociation energy (BDE) for (X-PhOH+PhO.-->X-PhO.+PhOH) led to logLD(50) (microM)=-0.601(+/-0.066)logP-0.040(+/-0.018)BDE+4.611(+/-0.166) (n=23, r(2)=0.827, s=0.223, P<0.05). Hydroquinone, catechol and 2-nitrophenol were outliers for the above equations. Using redox potential and logP led to a new correlation: logLD(50) (microM)=-0.529(+/-0.135)logP+2.077(+/-0.892)E(p/2)+2.806(+/-0.592) (n=15, r(2)=0.561, s=0.383, P<0.05) with 4-nitrophenol as an outlier. Our findings indicate that phenols with higher lipophilicity, BDE, or sigma+ values or with lower pK(a) and redox potential were more toxic towards hepatocytes. We also showed that a collapse of hepatocyte mitochondrial membrane potential preceded the cytotoxicity of most phenols. Our study indicates that one or a combination of mechanisms; i.e. mitochondrial uncoupling, phenoxy radicals, or phenol metabolism to quinone methides and quinones, contribute to phenol cytotoxicity towards hepatocytes depending on the phenol chemical structure.

Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis.

PubMed

Nesnow, Stephen; Nelson, Garret; Padgett, William T; George, Michael H; Moore, Tanya; King, Leon C; Adams, Linda D; Ross, Jeffrey A

2010-07-30

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-7,8-dihydroxy-7,8-dihydroB[a]P-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: (1) the induction of apurinic sites from radical cation processes, and (2) the metabolic formation of B[a]P-7,8-quinone (BPQ) that can form covalent DNA adducts or reactive oxygen species which can damage DNA. The studies presented here sought to examine the role of stable BPQ-DNA adducts in B[a]P-induced mouse lung tumorigenesis. Male strain A/J mice were injected intraperitoneally once with BPQ or trans-7,8-dihydroxy-7,8-dihydroB[a]P (BP-7,8-diol) at 30, 10, 3, or 0mg/kg. Lungs and livers were harvested after 24h, the DNA extracted and subjected to (32)P-postlabeling analysis. Additional groups of mice were dosed once with BPQ or BP-7,8-diol each at 30 mg/kg and tissues harvested 48 and 72 h later, or with B[a]P (50mg/kg, a tumorigenic dose) and tissues harvested 72 h later. No BPQ or any other DNA adducts were observed in lung or liver tissues 24, 48, or 72 h after the treatment with 30 mg/kg BPQ. BP-7,8-diol gave BPDE-DNA adducts at all time points in both tissues and B[a]P treatment gave BPDE-DNA adducts in the lung. In each case, no BPQ-DNA adducts were detected. Mouse body weights significantly decreased over time after BPQ or BP-7,8-diol treatments suggesting that systemic toxicity was induced by both agents. Model studies with BPQ and N-acetylcysteine suggested that BPQ is rapidly inactivated by sulfhydryl-containing compounds and not available for DNA adduction. We conclude that under these treatment conditions BPQ does not form stable covalent DNA adducts in the lungs or livers of strain A/J mice, suggesting that stable BPQ-covalent adducts are not a part of the complex of mechanisms involved in B[a]P-induced mouse lung tumorigenesis. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Vitamin E and vitamin E-quinone levels in red blood cells and plasma of newborn infants and their mothers.

PubMed

Jain, S K; Wise, R; Bocchini, J J

1996-02-01

Vitamin E is a physiological antioxidant and protects cell membranes from oxidative damage. This study has determined whether vitamin E level in RBC of newborns has any relationship with its level in their mothers. We have also examined levels of vitamin E and vitamin E-quinone, an oxidized product of vitamin E, in paired samples of red blood cells (RBC) and plasma of newborns and their mothers. Blood was collected from 26 mothers and their full-term placental cords at delivery. Vitamin E and vitamin E-quinone levels were determined in RBC and plasma by HPLC. Newborn-plasma had significantly lower vitamin E levels compared with maternal-plasma both when expressed as nmole/ml (5.5+/-0.4 vs 26.1+/-1.1, p = 0.0001) or nmole/mumole total lipids (1.9+/-0.1 vs 2.6+/-0.1, p = 0.0001). Vitamin E level in the newborn-RBC was similar to that of maternal-RBC when expressed as nmole/ml packed cells (2.77+/-0.14 vs 2.95+/-0.13), but was significantly lower when expressed as nmole/mumole total lipids (0.56+/-0.03 vs 0.64+/-0.04, p = 0.03) from that of maternal-RBC. Vitamin E-quinone levels are significantly elevated in newborns compared with their mothers both in RBC (29.4+/-2.1 vs 24.1+/-1.2, p = 0.04) and plasma (39.9+/-5.3 vs 25.3+/-4.2, p = 0.006) when expressed as nmole/mmole total lipids but not when expressed as nmole/ml. There was a significant correlation of vitamin E between newborn-plasma and newborn-RBC (r = 0.65, p = 0.0002 for nmole per ml packed RBC;r = 0.63, p = 0.0007 for nmole per mumole total lipids). The relationship between maternal plasma and newborn plasma was significant when vitamin E was normalized with nmole/mumole total lipid (r = 0.54, p = 0.007 but not when expressed as nmole/ml (r = 0.09, p = 0.64). However, vitamin E in the RBC of maternal and newborn had significant correlation when expressed as per ml packed cells (r = 0.61, p = 0.001) and per total lipid (r = 0.46, p = 0.02). There was no relationship of vitamin E-quinone levels between RBC and plasma of newborns and their mothers. Elevated blood levels of vitamin E-quinone suggest increased oxidative stress and utilization of vitamin E in newborns compared to their mothers. Because vitamin E levels in RBC of newborns are lower and significantly related to vitamin E levels in RBC of their mothers, an increase in vitamin E supplementation to mothers during pregnancy may increase vitamin E levels in the newborn and help impede the effect of extrauterine oxygen toxicity.

Phospholipid and Respiratory Quinone Analyses From Extreme Environments

NASA Astrophysics Data System (ADS)

Pfiffner, S. M.

2008-12-01

Extreme environments on Earth have been chosen as surrogate sites to test methods and strategies for the deployment of space craft in the search for extraterrestrial life. Surrogate sites for many of the NASA astrobiology institutes include the South African gold mines, Canadian subpermafrost, Atacama Desert, and acid rock drainage. Soils, sediments, rock cores, fracture waters, biofilms, and service and drill waters represent the types of samples collected from these sites. These samples were analyzed by gas chromatography mass spectrometry for phospholipid fatty acid methyl esters and by high performance liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry for respiratory quinones. Phospholipid analyses provided estimates of biomass, community composition, and compositional changes related to nutritional limitations or exposure to toxic conditions. Similar to phospholipid analyses, respiratory quinone analyses afforded identification of certain types of microorganisms in the community based on respiration and offered clues to in situ redox conditions. Depending on the number of samples analyzed, selected multivariate statistical methods were applied to relate membrane lipid results with site biogeochemical parameters. Successful detection of life signatures and refinement of methodologies at surrogate sites on Earth will be critical for the recognition of extraterrestrial life. At this time, membrane lipid analyses provide useful information not easily obtained by other molecular techniques.

Review of the taxonomy of the genus Arthrobacter, emendation of the genus Arthrobacter sensu lato, proposal to reclassify selected species of the genus Arthrobacter in the novel genera Glutamicibacter gen. nov., Paeniglutamicibacter gen. nov., Pseudoglutamicibacter gen. nov., Paenarthrobacter gen. nov. and Pseudarthrobacter gen. nov., and emended description of Arthrobacter roseus.

PubMed

Busse, Hans-Jürgen

2016-01-01

In this paper, the taxonomy of the genus Arthrobacter is discussed, from its first description in 1947 to the present state. Emphasis is given to intrageneric phylogeny and chemotaxonomic characteristics, concentrating on quinone systems, peptidoglycan compositions and polar lipid profiles. Internal groups within the genus Arthrobacter indicated from homogeneous chemotaxonomic traits and corresponding to phylogenetic grouping and/or high 16S rRNA gene sequence similarities are highlighted. Furthermore, polar lipid profiles and quinone systems of selected species are shown, filling some gaps concerning these chemotaxonomic traits. Based on phylogenetic groupings, 16S rRNA gene sequence similarities and homogeneity in peptidoglycan types, quinone systems and polar lipid profiles, a description of the genus Arthrobacter sensu lato and an emended description of Arthrobacter roseus are provided. Furthermore, reclassifications of selected species of the genus Arthrobacter into novel genera are proposed, namely Glutamicibacter gen. nov. (nine species), Paeniglutamicibacter gen. nov. (six species), Pseudoglutamicibacter gen. nov. (two species), Paenarthrobacter gen. nov. (six species) and Pseudarthrobacter gen. nov. (ten species).

Oxidation of atenolol, propranolol, carbamazepine and clofibric acid by a biological Fenton-like system mediated by the white-rot fungus Trametes versicolor.

PubMed

Marco-Urrea, Ernest; Radjenović, Jelena; Caminal, Gloria; Petrović, Mira; Vicent, Teresa; Barceló, Damià

2010-01-01

Biological advanced oxidation of the pharmaceuticals clofibric acid (CA), carbamazepine (CBZP), atenolol (ATL) and propranolol (PPL) is reported for the first time. Extracellular oxidizing species were produced through a quinone redox cycling mechanism catalyzed by an intracellular quinone reductase and any of the ligninolytic enzymes of Trametes versicolor after addition of the lignin-derived quinone 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe(3+)-oxalate in the medium. Time-course experiments with approximately 10mg L(-1) of initial pharmaceutical concentration resulted in percent degradations above 80% after 6h of incubation. Oxidation of pharmaceuticals was only observed under DBQ redox cycling conditions. A similar degradation pattern was observed when CBZP was added at the environmentally relevant concentration of 50 microg L(-1). Depletion of DBQ due to the attack of oxidizing agents was assumed to be the main limiting factor of pharmaceutical degradation. The main degradation products, that resulted to be pharmaceutical hydroxylated derivatives, were structurally elucidated. The detected 4- and 7-hydroxycarbamazepine intermediates of CBZP degradation were not reported to date. Total disappearance of intermediates was observed in all the experiments at the end of the incubation period. (c) 2009 Elsevier Ltd. All rights reserved.

Respiration metabolism of Group B Streptococcus is activated by environmental haem and quinone and contributes to virulence.

PubMed

Yamamoto, Yuji; Poyart, Claire; Trieu-Cuot, Patrick; Lamberet, Gilles; Gruss, Alexandra; Gaudu, Philippe

2005-04-01

Group B Streptococcus (GBS) is a common constituent of the vaginal microflora, but its transmission to newborns can cause life-threatening sepsis, pneumonia and meningitis. Energy metabolism of this opportunist pathogen has been deduced to be strictly fermentative. We discovered that GBS undergoes respiration metabolism if its environment supplies two essential respiratory components: quinone and haem. Respiration metabolism led to significant changes in growth characteristics, including a doubling of biomass and an altered metabolite profile under the tested conditions. The GBS respiratory chain is inactivated by: (i) withdrawing haem and/or quinone, (ii) treating cultures with a respiration inhibitor or (iii) inactivating the cydA gene product, a subunit of cytochrome bd quinol oxidase, in all cases resulting in exclusively fermentative growth. cydA inactivation reduced GBS growth in human blood and strongly attenuated virulence in a neonatal rat sepsis model, suggesting that the animal host may supply the components that activate GBS respiration. These results suggest a role of respiration metabolism in GBS dissemination. Our findings show that environmental factors can increase the flexibility of GBS metabolism by activating a newly identified respiration chain. The need for two environmental factors may explain why GBS respiration metabolism was not found in previous studies.

Cyanide as a copper and quinone-directed inhibitor of amine oxidases from pea seedlings ( Pisum sativum) and Arthrobacter globiformis: evidence for both copper coordination and cyanohydrin derivatization of the quinone cofactor.

PubMed

Shepard, Eric M; Juda, Gregory A; Ling, Ke-Qing; Sayre, Lawrence M; Dooley, David M

2004-04-01

The interactions of cyanide with two copper-containing amine oxidases (CuAOs) from pea seedlings (PSAO) and the soil bacterium Arthrobacter globiformis (AGAO) have been investigated by spectroscopic and kinetic techniques. Previously, we rationalized the effects of azide and cyanide for several CuAOs in terms of copper coordination by these exogenous ligands and their effects on the internal redox equilibrium TPQ(amr)-Cu(II) right harpoon over left harpoon TPQ(sq)-Cu(I). The mechanism of cyanide inhibition was proposed to occur through complexation to Cu(I), thereby directly competing with O(2) for reoxidation of TPQ. Although cyanide readily and reversibly reacts with quinones, no direct spectroscopic evidence for cyanohydrin derivatization of TPQ has been previously documented for CuAOs. This work describes the first direct spectroscopic evidence, using both model and enzyme systems, for cyanohydrin derivatization of TPQ. K(d) values for Cu(II)-CN(-) and Cu(I)-CN(-), as well as the K(i) for cyanide inhibition versus substrate amine, are reported for PSAO and AGAO. In spite of cyanohydrin derivatization of the TPQ cofactor in these enzymes, the uncompetitive inhibition of amine oxidation is determined to arise almost exclusively through CN(-) complexation of Cu(I).

Biomimetic Oxygen-Evolving Photobacteria Based on Amino Acid and Porphyrin Hierarchical Self-Organization.

PubMed

Liu, Kai; Zhang, Han; Xing, Ruirui; Zou, Qianli; Yan, Xuehai

2017-12-26

Biomimetic organization provides a promising strategy to develop functional materials and understand biological processes. However, how to mimic complex biological systems using simple biomolecular units remains a great challenge. Herein, we design and fabricate a biomimetic cyanobacteria model based on self-integration of small bioinspired molecules, including amphiphilic amino acid, 3,4-dihydroxyphenylalanine (DOPA), and metalloporphyrin and cobalt oxide nanoparticles (Co 3 O 4 NPs), with the assistance of chemical conjugation and molecular self-assembly. The assembled amino acid fiber can be modified by DOPA to form covalently bound DOPA melanin containing hydroxyl and quinone species via Schiff base reaction. The adhering template can further tune the self-assembly of metalloporphyrin and Co 3 O 4 NPs into J-aggregation and dispersive distribution, respectively, mainly via coordination binding. Metalloporphyrin molecules in the resulting hybrid fibers capture light; quinone species accept the excited electrons, and Co 3 O 4 NPs catalyze water oxidation. Thus, the essential components of the photosystem-II protein complex in cyanobacteria are simplified and engineered into a simple framework, still retaining a similar photosynthetic mechanism. In addition, this architecture leads to efficient coupling of antenna, quinone-type reaction center, and photocatalyst, which increases the flux of light energy from antenna to reaction center for charge separation, resulting in enhanced oxygen evolution rate with excellent sustainability.

Cation Effects on the Electron-Acceptor Side of Photosystem II.

PubMed

Khan, Sahr; Sun, Jennifer S; Brudvig, Gary W

2015-06-18

The normal pathway of electron transfer on the electron-acceptor side of photosystem II (PSII) involves electron transfer from quinone A, QA, to quinone B, QB. It is possible to redirect electrons from QA(-) to water-soluble Co(III) complexes, which opens a new avenue for harvesting electrons from water oxidation by immobilization of PSII on electrode surfaces. Herein, the kinetics of electron transfer from QA(-) to [Co(III)(terpy)2](3+) (terpy = 2,2';6',2″-terpyridine) are investigated with a spectrophotometric assay revealing that the reaction follows Michaelis-Menten saturation kinetics, is inhibited by cations, and is not affected by variation of the QA reduction potential. A negatively charged site on the stromal surface of the PSII protein complex, composed of glutamic acid residues near QA, is hypothesized to bind cations, especially divalent cations. The cations are proposed to tune the redox properties of QA through electrostatic interactions. These observations may thus explain the molecular basis of the effect of divalent cations like Ca(2+), Sr(2+), Mg(2+), and Zn(2+) on the redox properties of the quinones in PSII, which has previously been attributed to long-range conformational changes propagated from divalent cations binding to the Ca(II)-binding site in the oxygen-evolving complex on the lumenal side of the PSII complex.

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).

Chemical ecology of the luna moth : Effects of host plant on detoxification enzyme activity.

PubMed

Lindroth, R L

1989-07-01

The effects of food plant on larval performance and midgut detoxification enzymes were investigated in larvae of the luna moth,Actias luna. Neonate larvae were fed leaves of black cherry, cottonwood, quaking aspen, white willow, red oak, white oak, tulip tree, paper birch, black walnut, butternut, or shagbark hickory. First instar survival, larval duration, and pupal weights were monitored as indices of food quality. Midgut enzyme preparations from fifth instars were assayed for β-glucosidase, quinone reductase, polysubstrate monooxygenase, esterase, and glutathione transferase activities. Larval survival on seven of the 11 plant species, including several recorded host plants, was extremely poor. Larvae performed well, and quite similarly, on birch, walnut, butternut, and hickory. Activities of all enzyme systems except β-glucosidase were significantly influenced by larval host plant. Of the systems assayed, quinone reductase and glutathione transferase activities were especially high. Comparisons of these values with published values for other Lepidoptera support the hypothesis that these enzyme systems are involved in conferring tolerance to juglone and related quinones occurring in members of the plant family Juglandaceae. Results suggest that host plant utilization by luna is more specialized at the individual or population level than at the species level and that biochemical detoxification systems may play a role in such specialization.

Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells.

PubMed

Hatae, Noriyuki; Nakamura, Jun; Okujima, Tetsuo; Ishikura, Minoru; Abe, Takumi; Hibino, Satoshi; Choshi, Tominari; Okada, Chiaki; Yamada, Hiroko; Uno, Hidemitsu; Toyota, Eiko

2013-08-15

9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 μM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Simulation of the oxidative metabolism of diclofenac by electrochemistry/(liquid chromatography/)mass spectrometry.

PubMed

Faber, Helene; Melles, Daniel; Brauckmann, Christine; Wehe, Christoph Alexander; Wentker, Kristina; Karst, Uwe

2012-04-01

Diclofenac is a frequently prescribed drug for rheumatic diseases and muscle pain. In rare cases, it may be associated with a severe hepatotoxicity. In literature, it is discussed whether this toxicity is related to the oxidative phase I metabolism, resulting in electrophilic quinone imines, which can subsequently react with nucleophiles present in the liver in form of glutathione or proteins. In this work, electrochemistry coupled to mass spectrometry is used as a tool for the simulation of the oxidative pathway of diclofenac. Using this purely instrumental approach, diclofenac was oxidized in a thin layer cell equipped with a boron doped diamond working electrode. Sum formulae of generated oxidation products were calculated based on accurate mass measurements with deviations below 2 ppm. Quinone imines from diclofenac were detected using this approach. It could be shown for the first time that these quinone imines do not react with glutathione exclusively but also with larger molecules such as the model protein β-lactoglobulin A. A tryptic digest of the generated drug-protein adduct confirms that the protein is modified at the only free thiol-containing peptide. This simple and purely instrumental set-up offers the possibility of generating reactive metabolites of diclofenac and to assess their reactivity rapidly and easily.

Dissection of the Voltage Losses of an Acidic Quinone Redox Flow Battery

DOE PAGES

Chen, Qing; Gerhardt, Michael R.; Aziz, Michael J.

2017-03-28

We measure the polarization characteristics of a quinone-bromide redox flow battery with interdigitated flow fields, using electrochemical impedance spectroscopy and voltammetry of a full cell and of a half cell against a reference electrode. We find linear polarization behavior at 50% state of charge all the way to the short-circuit current density of 2.5 A/cm 2. We uniquely identify the polarization area-specific resistance (ASR) of each electrode, the membrane ASR to ionic current, and the electronic contact ASR. We use voltage probes to deduce the electronic current density through each sheet of carbon paper in the quinone-bearing electrode. By alsomore » interpreting the results using the Newman 1-D porous electrode model, we deduce the volumetric exchange current density of the porous electrode. We uniquely evaluate the power dissipation and identify a correspondence to the contributions to the electrode ASR from the faradaic, electronic, and ionic transport processes. We find that, within the electrode, more power is dissipated in the faradaic process than in the electronic and ionic conduction processes combined, despite the observed linear polarization behavior. We examine the sensitivity of the ASR to the values of the model parameters. The greatest performance improvement is anticipated from increasing the volumetric exchange current density.« less

Browning inhibition mechanisms by cysteine, ascorbic acid and citric acid, and identifying PPO-catechol-cysteine reaction products.

PubMed

Ali, Hussein M; El-Gizawy, Ahmed M; El-Bassiouny, Rawia E I; Saleh, Mahmoud A

2015-06-01

The titled compounds were examined as PPO inhibitors and antibrowning agents; their various mechanisms were investigated and discussed. All compounds reduced significantly both the browning process and PPO activity. Browning index gave strong correlation with PPO activity (r(2) = 0.96, n = 19) indicating that the browning process is mainly enzymatic. Ascorbic acid could reduce the formed quinone instantly to the original substrate (catechol) at high concentration (>1.5 %) while at lower concentrations acted as competitive inhibitor (KI = 0.256 ± 0.067 mM). Cysteine, at higher concentrations (≥1.0 %), reacted with the resulted quinone to give a colorless products while at the low concentrations, cysteine worked as competitive inhibitor (KI = 1.113 ± 0.176 mM). Citric acid acted only as PPO non-competitive inhibitor with KI = 2.074 ± 0.363 mM. The products of PPO-catechole-cysteine reaction could be separation and identification by LC-ESI-MS. Results indicated that the product of the enzymatic oxidation of catechol, quinone, undergoes two successive nucleophilic attacks by cysteine thiol group. Cysteine was condensed with the resulted mono and dithiocatechols to form peptide side chains.

Flow injection amperometric sensor with a carbon nanotube modified screen printed electrode for determination of hydroquinone.

PubMed

Upan, Jantima; Reanpang, Preeyaporn; Chailapakul, Orawon; Jakmunee, Jaroon

2016-01-01

Flow injection amperometric (FI-Amp) sensor was developed for sensitive and selective determination of hydroquinone. A simple screen printed carbon electrode (SPCE) was modified with various nanomaterials for improvement of sensitivity on the determination of quinone. As a result, the appropriate sensitivity is obtained from the SPCE modified with carbon nanotube (CNT) which indicated that CNT contributed to the transfer of electron to quinone. The reproducibility (n=9) and repeatability (n=111) of SPCE-CNT were obtained at 4.4% and 3.6%RSD, respectively. The SPCE-CNT electrode and enzymatic column were incorporated to the FI-Amp system to determine hydroquinone. Laccase was immobilized on silica gel using a cross-linking method by glutaraldehyde modification and then packed in the column. The laccase column has high efficiency for catalytic oxidation of hydroquinone to quinone, which further detects by amperometric detection. Parameters affecting response of the proposed sensor, i.e., pH, ionic strength, and temperature have been optimized. The proposed system provided a wide linear range between 1 and 50 µM with detection limit of 0.1 µM. Satisfactory recoveries in the range of 91.2-103.8% were obtained for the analysis of water sample. Copyright © 2015 Elsevier B.V. All rights reserved.

Further Insights on the Chemical Structure of Humic Substances (HS) and Chromophoric Dissolved Organic Matter (CDOM) in Relation to their Optical/Chemical Properties

NASA Astrophysics Data System (ADS)

Del Vecchio, R.; Schendorf, T. M.; Koech, K.; Blough, N. V.

2016-02-01

HS have been studied extensively over the last decades, yet the structural basis of their optical properties is still highly debated. Aromatic ketones, aldehydes and quinones along with carboxylic groups and phenolic moieties are significant constituents of HS, however their contribution to the optical properties has only recently been investigated. Chemical manipulation of selected functional groups thus represents an extremely promising approach to highlight the contribution of such groups to the HS (and CDOM) optical properties. Chemical reduction (and re-oxidation) along with pH titrations are employed herein to assess the relative contribution of aromatic ketones/aldehydes/quinones and carboxylic groups/phenolic moieties, respectively to the optical properties of HS (and CDOM). Results indicate that (a) the contribution of quinones to HS absorption and fluorescence is minor (or nil), while that of aromatic ketones (and aldehydes) is significant; (b) phenolic groups contribute more than carboxylic acids to the HS optical properties; (c) the effects of borohydride reduction and pH on the long-wavelength absorption and fluorescence is consistent with charge-transfer interactions between carbonyl and phenolic groups (as well as aromatic carboxylic acids, but to a smaller extent). Results will be presented within the context of our proposed charge-transfer model.

Investigation of the cumulative body burden of estrogen-3,4-quinone in breast cancer patients and controls using albumin adducts as biomarkers.

PubMed

Lin, Che; Chen, Dar-Ren; Hsieh, Wei-Chung; Yu, Wen-Fa; Lin, Ching-Chiuan; Ko, Mao-Huei; Juan, Chang-Hsin; Tsuang, Ben-Jei; Lin, Po-Hsiung

2013-04-26

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. Elevation of E2-3,4-Q to E2-2,3-Q ratio is thought to be an important indicator of estrogen-induced carcinogenesis. Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n=152) vs healthy controls (n=75) by using albumin (Alb) adducts as biomarkers. Results clearly demonstrated the presence of cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in all study population at levels ranging from 61.7-1330 to 66.6-1,590 pmol/g, respectively. Correlation coefficient between E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb was 0.610 for controls and 0.767 for breast cancer patients (p<0.001). We also noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levels of E2-3,4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E2-3,4-Q-2-S-Alb per 5 kg/m(2) decrease in BMI (p<0.001). In addition, we confirmed that mean levels of E2-3,4-Q-2-S-Alb in breast cancer patients were ∼5-fold greater than in those of controls (p<0.001). Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E2-3,4-Q may play a role in the development of breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Physiological responses of emerald ash borer larvae to feeding on different ash species reveal putative resistance mechanisms and insect counter-adaptations.

PubMed

Rigsby, C M; Showalter, D N; Herms, D A; Koch, J L; Bonello, P; Cipollini, D

2015-07-01

Emerald ash borer, Agrilus planipennis Fairmaire, an Asian wood-boring beetle, has devastated ash (Fraxinus spp.) trees in North American forests and landscapes since its discovery there in 2002. In this study, we collected living larvae from EAB-resistant Manchurian ash (Fraxinus mandschurica), and susceptible white (Fraxinus americana) and green (Fraxinus pennsylvanica) ash hosts, and quantified the activity and production of selected detoxification, digestive, and antioxidant enzymes. We hypothesized that differences in larval physiology could be used to infer resistance mechanisms of ash. We found no differences in cytochrome P450, glutathione-S-transferase, carboxylesterase, sulfotransferase, and tryptic BApNAase activities between larvae feeding on different hosts. Despite this, Manchurian ash-fed larvae produced a single isozyme of low electrophoretic mobility that was not produced in white or green ash-fed larvae. Additionally, larvae feeding on white and green ash produced two serine protease isozymes of high electrophoretic mobility that were not observed in Manchurian ash-fed larvae. We also found lower activity of β-glucosidase and higher activities of monoamine oxidase, ortho-quinone reductase, catalase, superoxide dismutase, and glutathione reductase in Manchurian ash-fed larvae compared to larvae that had fed on susceptible ash. A single isozyme was detected for both catalase and superoxide dismutase in all larval groups. The activities of the quinone-protective and antioxidant enzymes are consistent with the resistance phenotype of the host species, with the highest activities measured in larvae feeding on resistant Manchurian ash. We conclude that larvae feeding on Manchurian ash could be under quinone and oxidative stress, suggesting these may be potential mechanisms of resistance of Manchurian ash to EAB larvae, and that quinone-protective and antioxidant enzymes are important counter-adaptations of larvae for dealing with these resistance mechanisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxygen control of nif gene expression in Klebsiella pneumoniae depends on NifL reduction at the cytoplasmic membrane by electrons derived from the reduced quinone pool.

PubMed

Grabbe, Roman; Schmitz, Ruth A

2003-04-01

In Klebsiella pneumoniae, the flavoprotein, NifL regulates NifA mediated transcriptional activation of the N2-fixation (nif) genes in response to molecular O2 and ammonium. We investigated the influence of membrane-bound oxidoreductases on nif-regulation by biochemical analysis of purified NifL and by monitoring NifA-mediated expression of nifH'-'lacZ reporter fusions in different mutant backgrounds. NifL-bound FAD-cofactor was reduced by NADH only in the presence of a redox-mediator or inside-out vesicles derived from anaerobically grown K. pneumoniae cells, indicating that in vivo NifL is reduced by electrons derived from membrane-bound oxidoreductases of the anaerobic respiratory chain. This mechanism is further supported by three lines of evidence: First, K. pneumoniae strains carrying null mutations of fdnG or nuoCD showed significantly reduced nif-induction under derepressing conditions, indicating that NifL inhibition of NifA was not relieved in the absence of formate dehydrogenase-N or NADH:ubiquinone oxidoreductase. The same effect was observed in a heterologous Escherichia coli system carrying a ndh null allele (coding for NADH dehydrogenaseII). Second, studying nif-induction in K. pneumoniae revealed that during anaerobic growth in glycerol, under nitrogen-limitation, the presence of the terminal electron acceptor nitrate resulted in a significant decrease of nif-induction. The final line of evidence is that reduced quinone derivatives, dimethylnaphthoquinol and menadiol, are able to transfer electrons to the FAD-moiety of purified NifL. On the basis of these data, we postulate that under anaerobic and nitrogen-limited conditions, NifL inhibition of NifA activity is relieved by reduction of the FAD-cofactor by electrons derived from the reduced quinone pool, generated by anaerobic respiration, that favours membrane association of NifL. We further hypothesize that the quinol/quinone ratio is important for providing the signal to NifL.

Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calamini, Barbara; Santarsiero, Bernard D.; Boutin, Jean A.

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 certainmore » 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.« less

Profiling the NIH Small Molecule Repository for Compounds That Generate H2O2 by Redox Cycling in Reducing Environments

PubMed Central

2010-01-01

We have screened the Library of Pharmacologically Active Compounds (LOPAC) and the National Institutes of Health (NIH) Small Molecule Repository (SMR) libraries in a horseradish peroxidase–phenol red (HRP-PR) H2O2 detection assay to identify redox cycling compounds (RCCs) capable of generating H2O2 in buffers containing dithiothreitol (DTT). Two RCCs were identified in the LOPAC set, the ortho-naphthoquinone β-lapachone and the para-naphthoquinone NSC 95397. Thirty-seven (0.02%) concentration-dependent RCCs were identified from 195,826 compounds in the NIH SMR library; 3 singleton structures, 9 ortho-quinones, 2 para-quinones, 4 pyrimidotriazinediones, 15 arylsulfonamides, 2 nitrothiophene-2-carboxylates, and 2 tolyl hydrazides. Sixty percent of the ortho-quinones and 80% of the pyrimidotriazinediones in the library were confirmed as RCCs. In contrast, only 3.9% of the para-quinones were confirmed as RCCs. Fifteen of the 251 arylsulfonamides in the library were confirmed as RCCs, and since we screened 17,868 compounds with a sulfonamide functional group we conclude that the redox cycling activity of the arylsulfonamide RCCs is due to peripheral reactive enone, aromatic, or heterocyclic functions. Cross-target queries of the University of Pittsburgh Drug Discovery Institute (UPDDI) and PubChem databases revealed that the RCCs exhibited promiscuous bioactivity profiles and have populated both screening databases with significantly higher numbers of active flags than non-RCCs. RCCs were promiscuously active against protein targets known to be susceptible to oxidation, but were also active in cell growth inhibition assays, and against other targets thought to be insensitive to oxidation. Profiling compound libraries or the hits from screening campaigns in the HRP-PR H2O2 detection assay significantly reduce the timelines and resources required to identify and eliminate promiscuous nuisance RCCs from the candidates for lead optimization. PMID:20070233

Novel Spectroscopic and Electrochemical Sensors and Nanoprobes for the Characterization of Food and Biological Antioxidants.

PubMed

Apak, Reşat; Demirci Çekiç, Sema; Üzer, Ayşem; Çelik, Saliha Esin; Bener, Mustafa; Bekdeşer, Burcu; Can, Ziya; Sağlam, Şener; Önem, Ayşe Nur; Erçağ, Erol

2018-01-11

Since an unbalanced excess of reactive oxygen/nitrogen species (ROS/RNS) causes various diseases, determination of antioxidants that can counter oxidative stress is important in food and biological analyses. Optical/electrochemical nanosensors have attracted attention in antioxidant activity (AOA) assessment because of their increased sensitivity and selectivity. Optical sensors offer advantages such as low cost, flexibility, remote control, speed, miniaturization and on-site/in situ analysis. Electrochemical sensors using noble metal nanoparticles on modified electrodes better catalyze bioelectrochemical reactions. We summarize the design principles of colorimetric sensors and nanoprobes for food antioxidants (including electron-transfer based and ROS/RNS scavenging assays) and important milestones contributed by our laboratory. We present novel sensors and nanoprobes together with their mechanisms and analytical performances. Our colorimetric sensors for AOA measurement made use of cupric-neocuproine and ferric-phenanthroline complexes immobilized on a Nafion membrane. We recently designed an optical oxidant/antioxidant sensor using N , N -dimethyl- p -phenylene diamine (DMPD) as probe, from which ROS produced colored DMPD-quinone cationic radicals electrostatically retained on a Nafion membrane. The attenuation of initial color by antioxidants enabled indirect AOA estimation. The surface plasmon resonance absorption of silver nanoparticles as a result of enlargement of citrate-reduced seed particles by antioxidant addition enabled a linear response of AOA. We determined biothiols with Ellman reagent-derivatized gold nanoparticles.

Noninnocent Proton-Responsive Ligand Facilitates Reductive Deprotonation and Hinders CO 2 Reduction Catalysis in [Ru(tpy)(6DHBP)(NCCH 3 )] 2+ (6DHBP = 6,6'-(OH) 2 bpy)

DOE PAGES

Duan, Lele; Manbeck, Gerald F.; Kowalczyk, Marta; ...

2016-04-14

Ruthenium complexes with proton-responsive ligands [Ru(tpy)(nDHBP)(NCCH 3)](CF 3SO 3) 2 (tpy = 2,2':6',2"-terpyridine; nDHBP = n,n'-dihydroxy-2,2'-bipyridine, n = 4 or 6) were examined in this study for reductive chemistry and as catalysts for CO 2 reduction. Electrochemical reduction of [Ru(tpy)(nDHBP)(NCCH 3)] 2+ generates deprotonated species through interligand electron transfer in which the initially formed tpy radical anion reacts with a proton source to produce singly and doubly deprotonated complexes that are identical to those obtained by base titration. A third reduction (i.e., reduction of [Ru(tpy)(nDHBP–2H +)] 0) triggers catalysis of CO 2 reduction; however, the catalytic efficiency is strikingly lowermore » than that of unsubstituted [Ru(tpy)(bpy)(NCCH 3)] 2+ (bpy = 2,2'-bipyridine). Cyclic voltammetry, bulk electrolysis, and spectroelectrochemical infrared experiments suggest the reactivity of CO 2 at both the Ru center and the deprotonated quinone-type ligand. Lastly, the Ru carbonyl formed by the intermediacy of a metallocarboxylic acid is stable against reduction, and mass spectrometry analysis of this product indicates the presence of two carbonates formed by the reaction of DHBP–2H + with CO 2.« less

Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

NASA Astrophysics Data System (ADS)

De Almeida, Wagner B.; O'Malley, Patrick J.

2018-03-01

Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.

PubMed

La Marca, Margherita; Beffy, Pascale; Pugliese, Annalisa; Longo, Vincenzo

2013-01-01

Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus.

Novel Spectroscopic and Electrochemical Sensors and Nanoprobes for the Characterization of Food and Biological Antioxidants

PubMed Central

Apak, Reşat; Demirci Çekiç, Sema; Üzer, Ayşem; Çelik, Saliha Esin; Bener, Mustafa; Bekdeşer, Burcu; Can, Ziya; Sağlam, Şener; Önem, Ayşe Nur; Erçağ, Erol

2018-01-01

Since an unbalanced excess of reactive oxygen/nitrogen species (ROS/RNS) causes various diseases, determination of antioxidants that can counter oxidative stress is important in food and biological analyses. Optical/electrochemical nanosensors have attracted attention in antioxidant activity (AOA) assessment because of their increased sensitivity and selectivity. Optical sensors offer advantages such as low cost, flexibility, remote control, speed, miniaturization and on-site/in situ analysis. Electrochemical sensors using noble metal nanoparticles on modified electrodes better catalyze bioelectrochemical reactions. We summarize the design principles of colorimetric sensors and nanoprobes for food antioxidants (including electron-transfer based and ROS/RNS scavenging assays) and important milestones contributed by our laboratory. We present novel sensors and nanoprobes together with their mechanisms and analytical performances. Our colorimetric sensors for AOA measurement made use of cupric-neocuproine and ferric-phenanthroline complexes immobilized on a Nafion membrane. We recently designed an optical oxidant/antioxidant sensor using N,N-dimethyl-p-phenylene diamine (DMPD) as probe, from which ROS produced colored DMPD-quinone cationic radicals electrostatically retained on a Nafion membrane. The attenuation of initial color by antioxidants enabled indirect AOA estimation. The surface plasmon resonance absorption of silver nanoparticles as a result of enlargement of citrate-reduced seed particles by antioxidant addition enabled a linear response of AOA. We determined biothiols with Ellman reagent−derivatized gold nanoparticles. PMID:29324685

Bioactive screening and in vitro antioxidant assessment of Nauclea latifolia leaf decoction

NASA Astrophysics Data System (ADS)

Iheagwam, Franklyn Nonso; Nsedu, Emmanuel Israel; Kayode, Kazeem Oyindamola; Emiloju, Opeyemi Christianah; Ogunlana, Olubanke Olujoke; Chinedu, Shalom Nwodo

2018-04-01

The phytochemical constituents and antioxidant properties of Nauclea latifolia leaf decoction were investigated. Dried leaves were extracted in ethanol. Qualitative and quantitative phytochemical analysis was determined spectrometrically. The antioxidant activities were examined in vitro using 2,2-diphenyl-1-picrylhydrazyl radical, total antioxidant capacity and ferric reducing antioxidant power assays. Phytochemical screening confirmed the presence of flavonoids, alkaloids, anthocyanins, betacyanins, phenols, saponins, terpenoids, cardiac glycosides and quinones. The total lycopene, β-carotene, phenolics, flavonoid and alkaloid content were found to be 0.038 ± 0.01 mg CAE/g, 0.120 ± 0.04 mg CAE/g, 58.08 ± 0.58 mg GAE/g, 10.75 ± 0.17 mg RE/g and 0.32 ± 0.08% respectively. N. latifolia ethanol leaf extract demonstrated effective antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl with an IC50 of 2.58 ± 0.08 mg/mL compared to 0.86 ± 0.02 mg/mL and < 0.01 ± 0.01 mg/mL for butylated hydroxytoluene and ascorbic acid respectively. Total antioxidant capacity and ferric reducing antioxidant power of the extract were 73.81 ± 2.27 and 1314.45 ± 197.64 mg AAE/g respectively. Excellent positive correlations between the phenolic content and antioxidant activities of the extract were observed. The leaf of N. latifolia is of therapeutic value and may be exploited for its rich antioxidant components.

Clinical physiology and mechanism of dizocilpine (MK-801)

PubMed Central

Somanathan, Ratnasamy

2010-01-01

Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3′-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and anti-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties. PMID:20716924

Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

PubMed

Chen, Yuan; Li, Bin; Zhao, Ran-ran; Zhang, Hui-feng; Zhen, Chao; Guo, Li

2015-04-10

Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-carcinogenic activity of 6-methylsulfinylhexyl isothiocyanate-, an active anti-proliferative principal of wasabi (Eutrema wasabi Maxim.).

PubMed

Fuke, Y; Haga, Y; Ono, H; Nomura, T; Ryoyama, K

1997-11-01

Synthetic 4-methylsulfinylhexyl isothiocyanate (MITC)(a potent inducer of phase 2 detoxification enzymes from broccoli) and 6-MITC(a potent anti-proliferative principal from wasabi) slightly inhibited the induction of mouse skin tumor in a two-stage process of carcinogenesis (initiator, 9,10-dimethyl-1,2-benzanthracene; promotor,12-o-tetradecanoylphorbol-13-acetate), but the effect was not significant. Both compounds, however, significantly inhibited the mutation of skin resulting from topical applications of the carcinogens. When a murine hepatoma cell line, Hepa 1c1c7, was treated with 2-,4-,6- and 8-MITCs, they augmented the induction of its quinone reductase, one of the phase 2 detoxification enzymes in a concentration dependent manner, and the 4- and 6-MITCs were much more potent on the reduction of the enzyme than the 2- and 8-MITCs. All 2-, 4-, 6- and 8-MITCs suppressed the growth of murine tumor cells, their suppressive activities being proportional to the length of their methyl residue. They were also cytotoxic to mouse peritoneal exudate macrophages which were not proliferating in vitro, indicating that the cellular targets of isothiocyanate may not be dependent upon the cell cycle. In addition, all the 2-, 4-, 6- and 8-MITCs inhibited the production of nitric oxide (a potent radical carcinogen) by peritoneal macrophages.

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

Activation of Nrf2 target enzymes conferring protection against oxidative stress in PC12 cells by ginger principal constituent 6-shogaol.

PubMed

Peng, Shoujiao; Yao, Juan; Liu, Yaping; Duan, Dongzhu; Zhang, Xiaolong; Fang, Jianguo

2015-08-01

Natural compounds containing phenoxyl groups and/or Michael acceptor units appear to possess antioxidant and cytoprotective properties. The ginger principal constituent 6-shogaol (6-S) represents one of such compounds. In this study, we reported that 6-S efficiently scavenges various free radicals in vitro, and displays remarkable cytoprotection against oxidative stress-induced cell damage in the neuron-like rat pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-S significantly upregulates a series of phase II antioxidant molecules, such as glutathione, heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1, thioredoxin reductase 1, and thioredoxin 1. A mechanistic study revealed that 6-S enhanced the translocation of Nrf2 from the cytosol to the nucleus and knockdown of Nrf2 abolished such protection, indicating that this cytoprotection is mediated by the activation of the transcription factor Nrf2. Another ginger constituent 6-gingerol (6-G), having a similar structure of 6-S but lacking the alpha,beta-unsaturated ketone structure (Michael acceptor moiety), failed to shelter PC12 cells from oxidative stress. Our results demonstrate that 6-S is a novel small molecule activator of Nrf2 in PC12 cells, and suggest that 6-S might be a potential candidate for the prevention of oxidative stress-mediated neurodegenerative disorders.

Enzymatically and chemically oxidized lignin nanoparticles for biomaterial applications.

PubMed

Mattinen, Maija-Liisa; Valle-Delgado, Juan José; Leskinen, Timo; Anttila, Tuomas; Riviere, Guillaume; Sipponen, Mika; Paananen, Arja; Lintinen, Kalle; Kostiainen, Mauri; Österberg, Monika

2018-04-01

Cross-linked and decolorized lignin nanoparticles (LNPs) were prepared enzymatically and chemically from softwood Kraft lignin. Colloidal lignin particles (CLPs, ca. 200 nm) in a non-malodorous aqueous dispersion could be dried and redispersed in tetrahydrofuran (THF) or in water retaining their stability i.e. spherical shape and size. Two fungal laccases, Trametes hirsuta (ThL) and Melanocarpus albomyces (MaL) were used in the cross-linking reactions. Reactivity of ThL and MaL on Lignoboost™ lignin and LNPs was confirmed by high performance size exclusion chromatography (HPSEC) and oxygen consumption measurements with simultaneous detection of red-brown color due to the formation of quinones. Zeta potential measurements verified oxidation of LNPs via formation of surface-oriented carboxylic acid groups. Dynamic light scattering (DLS) revealed minor changes in the particle size distributions of LNPs after laccase catalyzed radicalization, indicating preferably covalent intraparticular cross-linking over polymerization. Changes in the surface morphology of laccase treated LNPs were imaged by atomic force (AFM) and transmission emission (TEM) microscopy. Furthermore, decolorization of LNPs without degradation was obtained using ultrasonication with H 2 O 2 in alkaline reaction conditions. The research results have high impact for the utilization of Kraft lignin as nanosized colloidal particles in advanced bionanomaterial applications in medicine, foods and cosmetics including different sectors from chemical industry. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Ecofriendly syntheses of phenothiazones and related structures facilitated by laccase – A comparative study

DOE PAGES

Cannatelli, Mark D.; Ragauskas, Arthur J.

2016-07-06

The biocatalytic synthesis of phenothiazones and related compounds has been achieved in an aqueous system under mild conditions facilitated by laccase oxidation. It was found that by coupling 2-aminothiophenol directly with 1,4-quinones, the product yields could be significantly increased compared to generating the 1,4-quinones in situ from the corresponding hydroquinones via laccase oxidation. However, laccase still proved to be pivotal for achieving highest product yields by catalyzing the final oxidation step. Furthermore, a difference in reactivity of aromatic and aliphatic amines toward 1,4-naphthoquinone is observed. Furthermore, this study provides a sustainable approach to the synthesis of a biologically important classmore » of compounds.« less

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.

Biochemistry of Catabolic Reductive Dehalogenation.

PubMed

Fincker, Maeva; Spormann, Alfred M

2017-06-20

A wide range of phylogenetically diverse microorganisms couple the reductive dehalogenation of organohalides to energy conservation. Key enzymes of such anaerobic catabolic pathways are corrinoid and Fe-S cluster-containing, membrane-associated reductive dehalogenases. These enzymes catalyze the reductive elimination of a halide and constitute the terminal reductases of a short electron transfer chain. Enzymatic and physiological studies revealed the existence of quinone-dependent and quinone-independent reductive dehalogenases that are distinguishable at the amino acid sequence level, implying different modes of energy conservation in the respective microorganisms. In this review, we summarize current knowledge about catabolic reductive dehalogenases and the electron transfer chain they are part of. We review reaction mechanisms and the role of the corrinoid and Fe-S cluster cofactors and discuss physiological implications.

Electrochemical analysis in a liposome suspension using lapachol as a hydrophobic electro active species.

PubMed

Okumura, Noriko; Wakamatsu, Shiori; Uno, Bunji

2014-01-01

This study demonstrated that the electro-chemical analysis of hydrophobic quinones can be performed in liposome suspension systems. We prepared and analyzed liposome suspensions containing lapachol, which is a quinone-based anti-tumor activity compound. In this suspension system, a simple one redox couple of lapachol is observed. These results are quite different from those obtained in organic solvents. In addition, the pH dependence of redox behaviors of lapachol could be observed in multilamellar vesicle (MLV) suspension system. This MLV suspension system method may approximate the electrochemical behavior of hydrophobic compounds in aqueous conditions. A benefit of this liposome suspension system for electrochemical analysis is that it enables to observe water-insoluble compounds without using organic solvents.

Sodium dodecyl benzene sulphonate mediated tautomerism of Eriochrome Black-T: Effect of charge transfer interaction

NASA Astrophysics Data System (ADS)

Ghosh, Sumit

2010-11-01

Interaction between anionic surfactant, sodium dodecyl benzene sulphonate, (SDBS) and an anionic dye Eriochrome Black-T, (EBT) has been investigated by visible spectroscopy, conductometry, dynamic light scattering and zeta potential measurements. Spectral changes of EBT observed on addition of SDBS indicate formation of quinone-hydrazone tautomer at pH 7.0, whereas in absence of SDBS this change appears at pH ˜ 9.45. However, at pH 7.0 this change in tautomerism is not observed in presence of sodium dodecyl sulphate (SDS). Experimental results indicate presence of charge transfer interaction between less stable quinone-hydrazone tautomer of EBT and SDBS molecules, which is confirmed using Benesi-Hildebrand and Scott equations.

Potential Chemopreventive Agents Based on the Structure of the Lead Compound 2-Bromo-1-hydroxyphenazine, Isolated from Streptomyces sp., Strain CNS284

PubMed Central

Conda-Sheridan, Martin; Marler, Laura; Park, Eun-Jung; Kondratyuk, Tamara P.; Jermihov, Katherine; Mesecar, Andrew D.; Pezzuto, John M.; Asolkar, Ratnakar N.; Fenical, William; Cushman, Mark

2010-01-01

The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces sp., strain CNS284, and its activity against NFκB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues be developed. Numerous phenazines were subsequently prepared and evaluated as inducers of quinone reductase 1 (QR1) and inhibitors of quinone reductase 2 (QR2), NF-κB, and inducible nitric oxide synthase (iNOS). Several of the active phenazine derivatives displayed IC50 values vs. QR1 induction and QR2 inhibition in the nanomolar range, suggesting they may find utility as cancer chemopreventive agents. PMID:21105712

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.

Oxidation of DJ-1 Induced by 6-Hydroxydopamine Decreasing Intracellular Glutathione

PubMed Central

Miyama, Akiko; Saito, Yoshiro; Yamanaka, Kazunori; Hayashi, Kojiro; Hamakubo, Takao; Noguchi, Noriko

2011-01-01

DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported to undergo preferential oxidation of the cysteine residue at position 106 (Cys-106) under oxidative stress; however, details of the molecular mechanisms are not well known. In the present study, mechanisms of DJ-1 oxidation induced by 6-hydroxydopamine (6-OHDA) were investigated by using SH-SY5Y cells. The treatment of these cells with 6-OHDA caused an obvious acidic spot sift of DJ-1 due to its oxidation. However, when catalase, which is an hydrogen peroxide (H2O2)-removing enzyme, was added during the treatment, it failed to prevent the oxidation induced by 6-OHDA, suggesting that electrophilic p-quinone formed from 6-OHDA, but not H2O2, was responsible for the DJ-1 oxidation. Benzoquinone, another electrophilic p-quinone, also induced DJ-1 oxidation. The intracellular glutathione (GSH) levels were significantly decreased by 6-OHDA, irrespective of the presence or absence of catalase. The inhibition of GSH synthesis by buthionine sulfoximine resulted in a decrease in GSH levels and enhancement of DJ-1 oxidation. The pretreatment of cells with N-acetyl-cysteine prevented the loss of intracellular GSH and subsequently DJ-1 oxidation induced by 6-OHDA. Collectively, these results suggest that electrophilic p-quinone formed from 6-OHDA induces DJ-1 oxidation by decreasing intracellular GSH. PMID:22132160

Identification of the ubiquinone-binding domain in the disulfide catalyst disulfide bond protein B.

PubMed

Xie, Tong; Yu, Linda; Bader, Martin W; Bardwell, James C A; Yu, Chang-An

2002-01-18

Disulfide bond (Dsb) formation is catalyzed in the periplasm of prokaryotes by the Dsb proteins. DsbB, a key enzyme in this process, generates disulfides de novo by using the oxidizing power of quinones. To explore the mechanism of this newly described enzymatic activity, we decided to study the ubiquinone-protein interaction and identify the ubiquinone-binding domain in DsbB by cross-linking to photoactivatable quinone analogues. When purified Escherichia coli DsbB was incubated with an azidoubiquinone derivative, 3-azido-2-methyl-5-[(3)H]methoxy-6-decyl-1,4-benzoquinone ([(3)H]azido-Q), and illuminated with long wavelength UV light, the decrease in enzymatic activity correlated with the amount of 3-azido-2-methyl-5-methoxy-6-decyl-1,4-benzoquinone (azido-Q) incorporated into the protein. One azido-Q-linked peptide with a retention time of 33.5 min was obtained by high performance liquid chromatography of the V8 digest of [(3)H]azido-Q-labeled DsbB. This peptide has a partial NH(2)-terminal amino acid sequence of NH(2)-HTMLQLY corresponding to residues 91-97. This sequence occurs in the second periplasmic domain of the inner membrane protein DsbB in a loop connecting transmembrane helices 3 and 4. We propose that the quinone-binding site is within or very near to this sequence.

Hydrogen Peroxide Activated Quinone Methide Precursors with Enhanced DNA Cross-Linking Capability and Cytotoxicity towards Cancer Cells

PubMed Central

Wang, Yibin; Fan, Heli; Balakrishnan, Kumudha; Lin, Zechao; Cao, Sheng; Chen, Wenbing; Fan, Yukai; Guthrie, Quibria A.; Sun, Huabing; Teske, Kelly A.; Gandhi, Varsha; Arnold, Leggy A.; Peng, Xiaohua

2017-01-01

Quinone methide (QM) formation induced by endogenously generated H2O2 is attractive for biological and biomedical applications. To overcome current limitations due to low biological activity of H2O2-activated QM precursors, we are introducing herein several new arylboronates with electron donating substituents at different positions of benzene ring and/or different neutral leaving groups. The reaction rate of the arylboronate esters with H2O2 and subsequent bisquinone methides formation and DNA cross-linking was accelerated with the application of Br as a leaving group instead of acetoxy groups. Additionally, a donating group placed meta to the nascent exo-methylene group of the quinone methide greatly improves H2O2-induced DNA interstrand cross-link formation as well as enhances the cellular activity. Multiple donating groups decrease the stability and DNA cross-linking capability, which lead to low cellular activity. A cell-based screen demonstrated that compounds 2a and 5a with a OMe or OH group dramatically inhibited the growth of various tissue-derived cancer cells while normal cells were less affected. Induction of H2AX phosphorylation by these compounds in CLL lymphocytes provide evidence for a correlation between cell death and DNA damage. The compounds presented herein showed potent anticancer activities and selectivity, which represent a novel scaffold for anticancer drug development. PMID:28388522

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

PubMed

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

Natural Abenquines and Their Synthetic Analogues Exert Algicidal Activity against Bloom-Forming Cyanobacteria.

PubMed

Nain-Perez, Amalyn; Barbosa, Luiz Cláudio Almeida; Maltha, Célia Regina Álvares; Forlani, Giuseppe

2017-04-28

Abenquines are natural quinones, produced by some Streptomycetes, showing the ability to inhibit cyanobacterial growth in the 1 to 100 μM range. To further elucidate their biological significance, the synthesis of several analogues (4f-h, 5a-h) allowed us to identify some steric and electronic requirements for bioactivity. Replacing the acetyl by a benzoyl group in the quinone core and also changing the amino acid moiety with ethylpyrimidinyl or ethylpyrrolidinyl groups resulted in analogues 25-fold more potent than the natural abenquines. The two most effective analogues inhibited the proliferation of five cyanobacterial strains tested, with IC 50 values ranging from 0.3 to 3 μM. These compounds may be useful leads for the development of an effective strategy for the control of cyanobacterial blooms.

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.

Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high-molecular-weight soluble polyphenolics of coffee.

PubMed

Kato, T; Takahashi, S; Kikugawa, K

1991-01-01

The presence of 2 kinds of components in brewed and instant coffee that could remove and destroy heterocyclic amine mutagens was demonstrated. The component that could remove the mutagens was insoluble fiber composed of hemicellulose. The fiber could tightly adsorb the mutagens Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C, and those generated in roasted coffee beans. The component that could destroy the mutagens was high-molecular-weight soluble polyphenolics. They might be converted into quinone derivatives in the presence of molecular oxygen. The quinone derivatives might destroy the mutagens. The fibers and the polyphenolics in one cup of brewed or instant coffee had the capacity to remove and destroy a substantial amount of the mutagens in pyrolysates of foodstuffs.

Combination of Aryl Diselenides/Hydrogen Peroxide and Carbon Nanotube-Rhodium Nanohybrid for Naphthols Oxidation: An Efficient Route towards Trypanocidal Quinones.

PubMed

de Carvalho, Renato L; Jardim, Guilherme A M; Santos, Augusto; Araujo, Maria H; Oliveira, Willian X C; Bombaça, Ana Cristina; Menna-Barreto, Rubem F S; Gopi, Elumalai; Gravel, Edmond; Doris, Eric; da Silva Júnior, Eufrânio Nunes

2018-06-14

We report a combination of aryl diselenides/hydrogen peroxide and carbon nanotube-rhodium nanohybrid for naphthols oxidation towards synthesis of 1,4-naphthoquinones and evaluation of their relevant trypanocidal activity. Under a combination of (PhSe)2/H2O2 in the presence of O2 in i-PrOH/Hexane, several benzenoid (A-ring) substituted quinones were prepared in moderate to high yields. We also studied the contribution of RhCNT as co-catalyst in this process and, in some cases, yields were improved. This method provides an efficient and versatile alternative for preparing A-ring modified naphthoquinonoid compounds with relevant biological profile. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

78 FR 21850 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... Parts 215, 235, and 237 Government procurement. Manuel Quinones, Editor, Defense Acquisition Regulations...-79 for notifying affected incumbent contractors of Government in-sourcing actions, in accordance with...

Principles, efficiency, and blueprint character of solar-energy conversion in photosynthetic water oxidation.

PubMed

Dau, Holger; Zaharieva, Ivelina

2009-12-21

Photosynthesis in plants and cyanobacteria involves two protein-cofactor complexes which are denoted as photosystems (PS), PSII and PSI. These solar-energy converters have powered life on earth for approximately 3 billion years. They facilitate light-driven carbohydrate formation from H(2)O and CO(2), by oxidizing the former and reducing the latter. PSII splits water in a process driven by light. Because all attractive technologies for fuel production driven by solar energy involve water oxidation, recent interest in this process carried out by PSII has increased. In this Account, we describe and apply a rationale for estimating the solar-energy conversion efficiency (eta(SOLAR)) of PSII: the fraction of the incident solar energy absorbed by the antenna pigments and eventually stored in form of chemical products. For PSII at high concentrations, approximately 34% of the incident solar energy is used for creation of the photochemistry-driving excited state, P680*, with an excited-state energy of 1.83 eV. Subsequent electron transfer results in the reduction of a bound quinone (Q(A)) and oxidation of the Tyr(Z) within 1 micros. This radical-pair state is stable against recombination losses for approximately 1 ms. At this level, the maximal eta(SOLAR) is 23%. After the essentially irreversible steps of quinone reduction and water oxidation (the final steps catalyzed by the PSII complex), a maximum of 50% of the excited-state energy is stored in chemical form; eta(SOLAR) can be as high as 16%. Extending our considerations to a photosynthetic organism optimized to use PSII and PSI to drive H(2) production, the theoretical maximum of the solar-energy conversion efficiency would be as high as 10.5%, if all electrons and protons derived from water oxidation were used for H(2) formation. The above performance figures are impressive, but they represent theoretical maxima and do not account for processes in an intact organism that lower these yields, such as light saturation, photoinhibitory, protective, and repair processes. The overpotential for catalysis of water oxidation at the Mn(4)Ca complex of PSII may be as low as 0.3 V. To address the specific energetics of water oxidation at the Mn complex of PSII, we propose a new conceptual framework that will facilitate quantitative considerations on the basis of oxidation potentials and pK values. In conclusion, photosynthetic water oxidation works at high efficiency and thus can serve as both an inspiring model and a benchmark in the development of future technologies for production of solar fuels.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breton, J.; Berger, G.; Nabedryk, E.

The photoreduction of the secondary quinone acceptor Q{sub B} in reaction centers (RCs) of the photosynthetic bacteria Rhodobacter sphaeroides and Rhodopseudomonas viridis has been investigated by light-induced FTIR difference spectroscopy of RCs reconstituted with several isotopically labeled ubiquinones. The labels used were {sup 18}O on both carbonyls and {sup 13}C either uniformly or selectively at the 1- or the 4-position, i.e., on either one of the two carbonyls. The Q{sub B}{sup {minus}}/Q{sub B} spectra of RCs reconstituted with the isotopically labeled and unlabeled quinones as well as the double differences calculated form these spectra exhibit distinct isotopic shifts for amore » numer of bands attributed to vibrations of Q{sub B} and Q{sub B}{sup {minus}}. The vibrational modes of the quinone in the Q{sub B} site are compared to those of ubiquinone in vitro, leading to band assignments for the C{double_bond}O and C{double_bond}C vibrations of the neutral Q{sub B} and for the C---O and C---C of the semiquinone. The C{double_bond}O frequency of each of the carbonyls of the unlabeled quinone is revealed at 1641 cm{sup {minus}1} for both species. This demonstrates symmetrical and weak hydrogen bonding of the two C{double_bond}O groups to the protein at the Q{sub B} site. In contrast, the C{double_bond}C vibrations are not equivalent for selective labeling at C{sub 1} or at C{sub 4}, although they both contribute to the {approximately}1611-cm{sup {minus}1} band in the Q{sub B}{sup {minus}}/Q{sub B} spectra of the two species. Compared to the vibrations of isolated ubiquinone, the C{double_bond}C mode of Q{sub B} does not involve displacement of the C{sub 4} carbon atom, while the motion of C{sub 1} is not hindered. Further analysis of the spectra suggests that the protein at the binding site imposes a specific constraint on the methoxy and/or the methyl group proximal to the C{sub 4} carbonyl. 49 refs., 5 figs.« less

Quinones are growth factors for the human gut microbiota.

PubMed

Fenn, Kathrin; Strandwitz, Philip; Stewart, Eric J; Dimise, Eric; Rubin, Sarah; Gurubacharya, Shreya; Clardy, Jon; Lewis, Kim

2017-12-20

The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.

Collapse of the native structure caused by a single amino acid exchange in human NAD(P)H:quinone oxidoreductase(1.).

PubMed

Lienhart, Wolf-Dieter; Gudipati, Venugopal; Uhl, Michael K; Binter, Alexandra; Pulido, Sergio A; Saf, Robert; Zangger, Klaus; Gruber, Karl; Macheroux, Peter

2014-10-01

Human quinone oxidoreductase 1 (NQO1) is essential for the antioxidant defense system, stabilization of tumor suppressors (e.g. p53, p33, and p73), and activation of quinone-based chemotherapeutics. Overexpression of NQO1 in many solid tumors, coupled with its ability to convert quinone-based chemotherapeutics into potent cytotoxic compounds, have made it a very attractive target for anticancer drugs. A naturally occurring single-nucleotide polymorphism (C609T) leading to an amino acid exchange (P187S) has been implicated in the development of various cancers and poor survival rates following anthracyclin-based adjuvant chemotherapy. Despite its importance for cancer prediction and therapy, the exact molecular basis for the loss of function in NQO1 P187S is currently unknown. Therefore, we solved the crystal structure of NQO1 P187S. Surprisingly, this structure is almost identical to NQO1. Employing a combination of NMR spectroscopy and limited proteolysis experiments, we demonstrated that the single amino acid exchange destabilized interactions between the core and C-terminus, leading to depopulation of the native structure in solution. This collapse of the native structure diminished cofactor affinity and led to a less competent FAD-binding pocket, thus severely compromising the catalytic capacity of the variant protein. Hence, our findings provide a rationale for the loss of function in NQO1 P187S with a frequently occurring single-nucleotide polymorphism. Structural data are available in the Protein Data Bank under the accession numbers 4cet (P187S variant with dicoumarol) and 4cf6 (P187S variant with Cibacron blue). NQO1 P187S and NQO1 P187S bind by nuclear magnetic resonance (View interaction) NQO1 P187S and NQO1 P187S bind by x-ray crystallography (1, 2) NQO1 and NQO1 bind by molecular sieving (1, 2). © 2014 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

77 FR 71185 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-29

... for-profit and not-for- profit institutions. Frequency: On occasion. Respondent's Obligation: Required..., 4800 Mark Center Drive, 2nd Floor, East Tower, Suite 02G09, Alexandria, VA 22350-3100. Manuel Quinones...

Tuning cofactor redox potentials: the 2-methoxy dihedral angle generates a redox potential difference of >160 mV between the primary (Q(A)) and secondary (Q(B)) quinones of the bacterial photosynthetic reaction center.

PubMed

Taguchi, Alexander T; Mattis, Aidas J; O'Malley, Patrick J; Dikanov, Sergei A; Wraight, Colin A

2013-10-15

Only quinones with a 2-methoxy group can act simultaneously as the primary (QA) and secondary (QB) electron acceptors in photosynthetic reaction centers from Rhodobacter sphaeroides. (13)C hyperfine sublevel correlation measurements of the 2-methoxy in the semiquinone states, SQA and SQB, were compared with quantum mechanics calculations of the (13)C couplings as a function of the dihedral angle. X-ray structures support dihedral angle assignments corresponding to a redox potential gap (ΔEm) between QA and QB of ~180 mV. This is consistent with the failure of a ubiquinone analogue lacking the 2-methoxy to function as QB in mutant reaction centers with a ΔEm of ≈160-195 mV.

Kinetic characterization of oxyresveratrol as a tyrosinase substrate.

PubMed

Ortiz-Ruiz, Carmen Vanessa; Ballesta de Los Santos, Manuel; Berna, Jose; Fenoll, Jose; Garcia-Ruiz, Pedro Antonio; Tudela, Jose; Garcia-Canovas, Francisco

2015-11-01

Oxyresveratrol is a stilbenoid described as a powerful inhibitor of tyrosinase and proposed as skin-whitening and anti-browning agent. However, the enzyme is capable of acting on it, considering it as a substrate, as it has been proved in the case of its analogous resveratrol. Tyrosinase hydroxylates the oxyresveratrol to an o-diphenol and oxidizes the latter to an o-quinone, which finally isomerizes to p-quinone. For these reactions to take place the presence of the Eox (oxy-tyrosinase) form is necessary. The kinetic analysis of the proposed mechanism has allowed the kinetic characterization of this molecule as a substrate of tyrosinase, affording a catalytic constant of 5.39 ± 0.21 sec(-1) and a Michaelis constant of 8.65 ± 0.73 µM. © 2015 International Union of Biochemistry and Molecular Biology.

Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones.

PubMed

Jardim, Guilherme A M; Silva, Thaissa L; Goulart, Marilia O F; de Simone, Carlos A; Barbosa, Juliana M C; Salomão, Kelly; de Castro, Solange L; Bower, John F; da Silva Júnior, Eufrânio N

2017-08-18

Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T. cruzi. We have identified fifteen compounds with IC 50 /24 h values of less than 2 μM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The oxidation of apomorphine and other catechol compounds by horseradish peroxidase: relevance to the measurement of dihydropteridine reductase activity.

PubMed

Milstien, S; Kaufman, S

1987-03-19

It has been reported by Shen et al. (Shen, R.-S., Smith, R.V., Davis, P.J. and Abell, C.W. (1984) J. Biol. Chem. 259, 8894-9000) that apomorphine and dopamine are potent, non-competitive inhibitors of quinonoid dihydropteridine reductase. In this paper we show that apomorphine, dopamine and other catechol-containing compounds are oxidized rapidly to quinones by the horseradish peroxidase-H2O2 system which is used to generate the quinonoid dihydropterin substrate. These quinones react non-enzymatically with reduced pyridine nucleotides, depleting the other substrate of dihydropteridine reductase. When true initial rates of dihydropteridine reductase-dependent reduction of quinonoid dihydropterins are measured, neither apomorphine nor any other catechol-containing compound that has been tested has been found to inhibit dihydropteridine reductase.

Structural and Biochemical Characterization of Chlamydia trachomatis Hypothetical Protein CT263 Supports That Menaquinone Synthesis Occurs through the Futalosine Pathway*

PubMed Central

Barta, Michael L.; Thomas, Keisha; Yuan, Hongling; Lovell, Scott; Battaile, Kevin P.; Schramm, Vern L.; Hefty, P. Scott

2014-01-01

The obligate intracellular human pathogen Chlamydia trachomatis is the etiological agent of blinding trachoma and sexually transmitted disease. Genomic sequencing of Chlamydia indicated this medically important bacterium was not exclusively dependent on the host cell for energy. In order for the electron transport chain to function, electron shuttling between membrane-embedded complexes requires lipid-soluble quinones (e.g. menaquionone or ubiquinone). The sources or biosynthetic pathways required to obtain these electron carriers within C. trachomatis are poorly understood. The 1.58Å crystal structure of C. trachomatis hypothetical protein CT263 presented here supports a role in quinone biosynthesis. Although CT263 lacks sequence-based functional annotation, the crystal structure of CT263 displays striking structural similarity to 5′-methylthioadenosine nucleosidase (MTAN) enzymes. Although CT263 lacks the active site-associated dimer interface found in prototypical MTANs, co-crystal structures with product (adenine) or substrate (5′-methylthioadenosine) indicate that the canonical active site residues are conserved. Enzymatic characterization of CT263 indicates that the futalosine pathway intermediate 6-amino-6-deoxyfutalosine (kcat/Km = 1.8 × 103 m−1 s−1), but not the prototypical MTAN substrates (e.g. S-adenosylhomocysteine and 5′-methylthioadenosine), is hydrolyzed. Bioinformatic analyses of the chlamydial proteome also support the futalosine pathway toward the synthesis of menaquinone in Chlamydiaceae. This report provides the first experimental support for quinone synthesis in Chlamydia. Menaquinone synthesis provides another target for agents to combat C. trachomatis infection. PMID:25253688

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.

Isolation and partial characterization of pigment-like antibiotics produced by a new strain of Streptosporangium isolated from an Algerian soil.

PubMed

Boudjella, H; Bouti, K; Zitouni, A; Mathieu, F; Lebrihi, A; Sabaou, N

2007-07-01

Identification of a new actinomycete strain Sg3, belonging to the genus Streptosporangium and partial characterization of the produced antibacterial activities. The strain Sg3 was isolated from an Algerian Saharan soil and identified by morphological, chemotaxonomic and phylogenetic analyses to the genus Streptosporangium. The comparison of its physiological characteristics with those of known species of Streptosporangium showed significant differences with the nearest species Streptosporangium carneum. Analysis of the 16S rDNA sequence of strain Sg3 showed a similarity level ranging between 97% and 98.8% within Streptosporangium species, with S. carneum the most closely related. Strain Sg3 showed a red coloured antibacterial activity against gram-positive bacteria on several culture media. The purification of the red pigment by chromatographic methods led to the isolation of three active products. The (1)H nuclear magnetic resonance (NMR), mass, infrared (IR) and ultraviolet-visible (UV-VIS) data of these molecules strongly suggested that they belonged to the quinone-anthracycline group with three or more rings. Strain Sg3 represents a distinct phyletic line suggesting a new genomic species. It produces antibacterial activities identified as quinone-anthracycline aromatics. The quinone-anthracycline antibiotics are known for their antimicrobial and antineoplastic activities and are used in chemotherapy for the treatment of many cancer diseases. The present work constitutes the first stage of a whole series of studies to be realized on these antibiotics before arriving at a possible application.

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar

PubMed Central

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-01-01

Objective To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Methods Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Results Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) µg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) µg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. Conclusions The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. PMID:24075342

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar.

PubMed

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-10-01

To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) μg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

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.

YNL134C from Saccharomyces cerevisiae encodes a novel protein with aldehyde reductase activity for detoxification of furfural derived from lignocellulosic biomass.

PubMed

Zhao, Xianxian; Tang, Juan; Wang, Xu; Yang, Ruoheng; Zhang, Xiaoping; Gu, Yunfu; Li, Xi; Ma, Menggen

2015-05-01

Furfural and 5-hydroxymethylfurfural (HMF) are the two main aldehyde compounds derived from pentoses and hexoses, respectively, during lignocellulosic biomass pretreatment. These two compounds inhibit microbial growth and interfere with subsequent alcohol fermentation. Saccharomyces cerevisiae has the in situ ability to detoxify furfural and HMF to the less toxic 2-furanmethanol (FM) and furan-2,5-dimethanol (FDM), respectively. Herein, we report that an uncharacterized gene, YNL134C, was highly up-regulated under furfural or HMF stress and Yap1p and Msn2/4p transcription factors likely controlled its up-regulated expression. Enzyme activity assays showed that YNL134C is an NADH-dependent aldehyde reductase, which plays a role in detoxification of furfural to FM. However, no NADH- or NADPH-dependent enzyme activity was observed for detoxification of HMF to FDM. This enzyme did not catalyse the reverse reaction of FM to furfural or FDM to HMF. Further studies showed that YNL134C is a broad-substrate aldehyde reductase, which can reduce multiple aldehydes to their corresponding alcohols. Although YNL134C is grouped into the quinone oxidoreductase family, no quinone reductase activity was observed using 1,2-naphthoquinone or 9,10-phenanthrenequinone as a substrate, and phylogenetic analysis indicates that it is genetically distant to quinone reductases. Proteins similar to YNL134C in sequence from S. cerevisiae and other microorganisms were phylogenetically analysed. Copyright © 2015 John Wiley & Sons, Ltd.

Kinetics and mechanism of hydration of o-thioquinone methide in aqueous solution. Rate-determining protonation of sulfur.

PubMed

Chiang, Yvonne; Kresge, A Jerry; Sadovski, Oleg; Zhan, Hao-Qiang

2005-03-04

o-Thioquinone methide, 2, was generated in aqueous solution by flash photolysis of benzothiete, 1, and rates of hydration of this quinone methide to o-mercaptobenzyl alcohol, 3, were measured in perchloric acid solutions, using H2O and D2O as the solvent, and also in acetic acid and tris(hydroxymethyl)methylammonium ion buffers, using H2O as the solvent. The rate profiles constructed from these data show hydronium-ion-catalyzed and uncatalyzed hydration reaction regions, just like the rate profiles based on literature data for hydration of the oxygen analogue, o-quinone methide, of the presently examined substrate. Solvent isotope effects on hydronium-ion catalysis of hydration for the two substrates, however, are quite different: k(H)/k(D) = 0.42 for the oxygen quinone methide, whereas k(H)/k(D) = 1.66 for the sulfur substrate. The inverse nature (k(H)/k(D) < 1) of the isotope effect in the oxygen system indicates that this reaction occurs by a preequilibrium proton-transfer reaction mechanism, with protonation of the substrate on its oxygen atom being fast and reversible and capture of the benzyl-type carbocationic intermediate so formed being rate-determining. The normal direction (k(H)/k(D) > 1) of the isotope effect in the sulfur system, on the other hand, suggests that protonation of the substrate on its sulfur atom is in this case rate-determining, with carbocation capture a fast following step. A semiquantitative argument supporting this hypothesis is presented.

Medium-dependent interactions of quinones with cytosine and cytidine: a laser flash photolysis study with magnetic field effect.

PubMed

Bose, Adity; Basu, Samita

2009-03-01

Laser flash photolysis and an external magnetic field have been used for the study of the interaction of two quinone molecules, namely, 9,10-anthraquinone (AQ) and 2-methyl 1,4-naphthoquinone (or menadione, MQ) with a DNA base, cytosine (C) and its nucleoside cytidine (dC) in two media, a homogeneous one composed of acetonitrile/water (ACN/H(2)O, 9:1, v/v) and a SDS micellar heterogeneous one. We have applied an external magnetic field for the proper identification of the transients formed during the interactions in micellar media. Cytosine exhibits electron transfer (ET) followed by hydrogen abstraction (HA) while dC reveals a reduced ET compared to C, with both quinones in organic homogeneous medium (ACN/H(2)O). Due to a higher electron affinity, AQ supports more faciler ET than MQ with dC in ACN/H(2)O but observations in SDS have been just the reverse. In SDS, ET from dC is completely quenched and a dominant HA is all that could be discerned. This work reveals two main findings: first, a drop in ET on addition of a ribose unit to C, which has been attributed to a role of keto-enol tautomerism in inducing ET from electron-rich nucleus and second, the effect of medium in controlling reaction mechanism by favoring HA with AQ although it is intrinsically more prone towards ET.

Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

PubMed Central

Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

2013-01-01

The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

Identification of a multi-protein reductive dehalogenase complex in Dehalococcoides mccartyi strain CBDB1 suggests a protein-dependent respiratory electron transport chain obviating quinone involvement.

PubMed

Kublik, Anja; Deobald, Darja; Hartwig, Stefanie; Schiffmann, Christian L; Andrades, Adarelys; von Bergen, Martin; Sawers, R Gary; Adrian, Lorenz

2016-09-01

Dehalococcoides mccartyi strain CBDB1 is an obligate organohalide-respiring bacterium using only hydrogen as electron donor and halogenated organics as electron acceptor. Here, we studied proteins involved in the respiratory chain under non-denaturing conditions. Using blue native gel electrophoresis (BN-PAGE), gel filtration and ultrafiltration an active dehalogenating protein complex with a molecular mass of 250-270 kDa was identified. The active subunit of reductive dehalogenase (RdhA) colocalised with a complex iron-sulfur molybdoenzyme (CISM) subunit (CbdbA195) and an iron-sulfur cluster containing subunit (CbdbA131) of the hydrogen uptake hydrogenase (Hup). No colocalisation between the catalytically active subunits of hydrogenase and reductive dehalogenase was found. By two-dimensional BN/SDS-PAGE the stability of the complex towards detergents was assessed, demonstrating stepwise disintegration with increasing detergent concentrations. Chemical cross-linking confirmed the presence of a higher molecular mass reductive dehalogenase protein complex composed of RdhA, CISM I and Hup hydrogenase and proved to be a potential tool for stabilising protein-protein interactions of the dehalogenating complex prior to membrane solubilisation. Taken together, the identification of the respiratory dehalogenase protein complex and the absence of indications for quinone participation in the respiration suggest a quinone-independent protein-based respiratory electron transfer chain in D. mccartyi. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Natural organic matter as electron acceptor: experimental evidence for its important role in anaerobic respiration

NASA Astrophysics Data System (ADS)

Lau, Maximilian Peter; Sander, Michael; Gelbrecht, Jörg; Hupfer, Michael

2014-05-01

Microbial respiration is a key driver of element cycling in oxic and anoxic environments. Upon depletion of oxygen as terminal electron acceptor (TEA), a number of anaerobic bacteria can employ alternative TEA for intracellular energy generation. Redox active quinone moieties in dissolved organic matter (DOM) are well known electron acceptors for microbial respiration. However, it remains unclear whether quinones in adsorbed and particulate OM accept electrons in a same way. In our studies we aim to understand the importance of natural organic matter (NOM) as electron acceptors for microbial energy gain and its possible implications for methanogenesis. Using a novel electrochemical approach, mediated electrochemical reduction and -oxidation, we can directly quantify reduced hydroquinone and oxidized quionone moieties in dissolved and particulate NOM samples. In a mesocosm experiment, we rewetted sediment and peat soil and followed electron transfer to the inorganic and organic electron acceptors over time. We found that inorganic and organic electron acceptor pools were depleted over the same timescales. More importantly, we showed that organic, NOM-associated electron accepting moieties represent as much as 21 40% of total TEA inventories. These findings support earlier studies that propose that the reduction of quinone moieties in particulate organic matter competitively suppresses methanogenesis in wetland soils. Our results indicate that electron transfer to organic, particulate TEA in inundated ecosystems has to be accounted for when establishing carbon budgets in and projecting greenhouse gas emissions from these systems.

A rhodium(III) complex for high-affinity DNA base-pair mismatch recognition

PubMed Central

Junicke, Henrik; Hart, Jonathan R.; Kisko, Jennifer; Glebov, Oleg; Kirsch, Ilan R.; Barton, Jacqueline K.

2003-01-01

A rhodium(III) complex, rac-[Rh(bpy)2phzi]3+ (bpy, 2,2′-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a sterically demanding intercalator targeted to destabilized mismatched sites in double-helical DNA. The complex is readily synthesized by condensation of the phenazine quinone with the corresponding diammine complex. Upon photoactivation, the complex promotes direct strand scission at single-base mismatch sites within the DNA duplex. As with the parent mismatch-specific reagent, [Rh(bpy)2(chrysi)]3+ [chrysene-5,6-quinone diimine (chrysi)], mismatch selectivity depends on the helix destabilization associated with mispairing. Unlike the parent chrysi complex, the phzi analogue binds and cleaves with high affinity and efficiency. The specific binding constants for CA, CC, and CT mismatches within a 31-mer oligonucleotide duplex are 0.3, 1, and 6 × 107 M−1, respectively; site-specific photocleavage is evident at nanomolar concentrations. Moreover, the specificity, defined as the ratio in binding affinities for mispaired vs. well paired sites, is maintained. The increase in affinity is attributed to greater stability in the mismatched site associated with stacking by the heterocyclic aromatic ligand. The high-affinity complex is also applied in the differential cleavage of DNA obtained from cell lines deficient in mismatch repair vs. those proficient in mismatch repair. Agreement is found between photocleavage by the mismatch-specific probes and deficiency in mismatch repair. This mismatch-specific targeting, therefore, offers a potential strategy for new chemotherapeutic design. PMID:12610209

Catalytic performance of quinone and graphene-modified polyurethane foam on the decolorization of azo dye Acid Red 18 by Shewanella sp. RQs-106.

PubMed

Zhou, Yang; Lu, Hong; Wang, Jing; Zhou, Jiti; Leng, Xueying; Liu, Guangfei

2018-08-15

Quinone-modified graphene powder is not reusable in bio-treatment systems, and the roles of quinone and graphene during extracellular electron-transfer processes remain unclear. In this study, we prepared anthraquinone-2-sulfonate and reduced graphene-oxide-modified polyurethane foam (AQS-rGO-PUF) and found that AQS-rGO-PUF exhibited higher catalytic performance on Acid Red 18 (AR 18) bio-decolorization compared with AQS-PUF and rGO-PUF. We observed a significant synergistic effect between AQS and rGO in AQS-rGO-PUF-mediated system in the presence of 50 μM AQS and 1.63 mg/L rGO. The synergistic effect was mainly attributed to electron transfer from AQS to rGO either directly or via flavins secreted by strain RQs-106, and ultimately to AR 18, accounting for ∼33.47% of AR 18 removal during AQS-rGO-PUF-mediated decolorization. Additionally, AQS-rGO-PUF exhibited good mechanical properties and maintained its macroporous structure. Furthermore, after eight rounds of experiments using AQS-rGO-PUF, the bio-decolorization efficiency of AR 18 retained >98.18% of its original value. These results indicate that the combination of AQS-rGO-PUF and Shewanella strains show potential efficacy for enhancing the treatment of azo-dye-containing wastewater. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Toxic effects of carvacrol, caryophyllene oxide, and ascaridole from essential oil of Chenopodium ambrosioides on mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monzote, Lianet; Stamberg, Werner; Staniek, Katrin

2009-11-01

Chenopodium ambrosioides have been used for centuries in the Americas as a popular remedy for parasitic diseases. The essential oil of this plant possesses anthelmintic activity and is still used in some regions to treat parasitosis and leishmaniasis. However, the Chenopodium oil caused also some fatalities, leading to its commercial disuse. In this work, we studied the mechanism of toxicity of the essential oil and its major pure ingredients (carvacrol, caryophyllene oxide, and ascaridole, which was synthesized from alpha-terpinene) with respect to mammalian cells and mitochondria. We observed that all products, but especially caryophyllene oxide, inhibited the mitochondrial electron transportmore » chain. This effect for carvacrol and caryophyllene oxide was mediated via direct complex I inhibition. Without Fe{sup 2+}, ascaridole was less toxic to mammalian mitochondria than other major ingredients. However, evidence on the formation of carbon-centered radicals in the presence of Fe{sup 2+} was obtained by ESR spin-trapping. Furthermore, it was shown that Fe{sup 2+} potentiated the toxicity of ascaridole on oxidative phosphorylation of rat liver mitochondria. The increase of the alpha-tocopherol quinone/alpha-tocopherol ratio under these conditions indicated the initiation of lipid peroxidation by Fe{sup 2+}-mediated ascaridole cleavage. Further ESR spin-trapping experiments demonstrated that in addition to Fe{sup 2+}, reduced hemin, but not mitochondrial cytochrome c can activate ascaridole, explaining why ascaridole in peritoneal macrophages from BALB/c mice exhibited a higher toxicity than in isolated mitochondria.« less

Photoionization of oxidized coenzyme Q in microemulsion: laser flash photolysis study in biomembrane-like system.

PubMed

Li, Kun; Wang, Mei; Wang, Jin; Zhu, Rongrong; Sun, Dongmei; Sun, Xiaoyu; Wang, Shi-Long

2013-01-01

Photoexcitation to generate triplet state has been proved to be the main photoreaction in homogeneous system for many benzoquinone derivatives, including oxidized coenzyme Q (CoQ) and its analogs. In the present study, microemulsion of CoQ, a heterogeneous system, is employed to mimic the distribution of CoQ in biomembrane. The photochemistry of CoQ(10) in microemulsion and cyclohexane is investigated and compared using laser flash photolysis and results show that CoQ(10) undergoes photoionization via a monophotonic process to generate radical cation of CoQ(10) in microemulsion and photoexcitation to generate excited triplet state in cyclohexane. Meanwhile, photoreactions of duroquinone (DQ) and CoQ(0) in microemulsion are also investigated to analyze the influence of molecular structure on the photochemistry of benzoquinone derivatives in microemulsion. Results suggest that photoexcitation, which is followed by excited state-involved hydrogen-abstraction reaction, is the main photoreaction for DQ and CoQ(0) in microemulsion. However, photoexcited CoQ(0) also leads to the formation of hydrated electrons. The isoprenoid side chain-involved high resonance stabilization is proposed to explain the difference in photoreactions of CoQ(0) and CoQ(10) in microemulsion. Considering that microemulsion is close to biomembrane system, its photoionization in microemulsion may be helpful to understand the real photochemistry of biological quinones in biomembrane system. © 2012 Tongji University. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure-activity relationship study.

PubMed

Ho, Si-Han Sherman; Sim, Mei-Yi; Yee, Wei-Loong Sherman; Yang, Tianming; Yuen, Shyi-Peng John; Go, Mei-Lin

2015-11-02

The anticancer agent YM155 is widely investigated as a specific survivin suppressant. More recently, YM155 was found to induce DNA damage and this has raised doubts as to whether survivin is its primary target. In an effort to assess the contribution of DNA damage to the anticancer activity of YM155, several analogs were prepared and evaluated for antiproliferative activity on malignant cells, participation in DNA intercalation and free radical generation by redox cycling. The intact positively charged scaffold was found to be essential for antiproliferative activity and intercalation but was less critical for redox cycling where the minimal requirement was a pared down bicyclic quinone. Side chain requirements at the N(1) and N(3) positions of the scaffold were more alike for redox cycling and intercalation than antiproliferative activity, underscoring yet again, the limited structural overlaps for these activities. Furthermore, antiproliferative activities were poorly correlated to DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23 nM), exceeding that of YM155, was found for a minimally substituted methyl analog AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA intercalator but with weak redox cycling activity. Thus, the capacity of this scaffold to inflict direct DNA damage leading to cell death may not be significant and YM155 should not be routinely classified as a DNA damaging agent. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Evaluation of the cytotoxic and antimutagenic effects of biflorin, an antitumor 1,4 o-naphthoquinone isolated from Capraria biflora L.

PubMed

Vasconcellos, Marne C; Moura, Dinara J; Rosa, Renato M; Machado, Miriana S; Guecheva, Temenouga N; Villela, Izabel; Immich, Bruna F; Montenegro, Raquel C; Fonseca, Aluísio M; Lemos, Telma L G; Moraes, Maria Elisabete A; Saffi, Jenifer; Costa-Lotufo, Letícia V; Moraes, Manoel O; Henriques, João A P

2010-10-01

Biflorin is a natural quinone isolated from Capraria biflora L. Previous studies demonstrated that biflorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective effects of biflorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using different approaches. In the Salmonella/microsome assay, biflorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biflorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biflorin did not induce significant mutagenic and recombinogenic effects at the employed concentration range. In addition, the pre-treatment with biflorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H(2)O(2)) in S. cerevisiae. In V79 mammalian cells, biflorin was cytotoxic at higher concentrations. Moreover, at low concentrations biflorin pre-treatment protected against H(2)O(2)-induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modified comet assay using DNA glycosylases. Our results suggest that biflorin cellular effects are concentration dependent. At lower concentrations, biflorin has significant antioxidant and protective effects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H(2)O(2) in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biflorin is cytotoxic and genotoxic.

Oxidation of phenolic endocrine disrupting chemicals by potassium permanganate in synthetic and real waters.

PubMed

Jiang, Jin; Pang, Su-Yan; Ma, Jun; Liu, Huiling

2012-02-07

In this study, five selected environmentally relevant phenolic endocrine disrupting chemicals (EDCs), estrone, 17β-estradiol, estriol, 17α-ethinylestradiol, and 4-n-nonylphenol, were shown to exhibit similarly appreciable reactivity toward potassium permanganate [Mn(VII)] with a second-order rate constant at near neutral pH comparable to those of ferrate(VI) and chlorine but much lower than that of ozone. In comparison with these oxidants, however, Mn(VII) was much more effective for the oxidative removal of these EDCs in real waters, mainly due to the relatively high stability of Mn(VII) therein. Mn(VII) concentrations at low micromolar range were determined by an ABTS [2,2-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid diammonium] spectrophotometric method based on the stoichiometric reaction of Mn(VII) with ABTS [Mn(VII) + 5ABTS → Mn(II) + 5ABTS(•+)] forming a stable green radical cation (ABTS(•+)). Identification of oxidation products suggested the initial attack of Mn(VII) at the hydroxyl group in the aromatic ring of EDCs, leading to a series of quinone-like and ring-opening products. The background matrices of real waters as well as selected model ligands including phosphate, pyrophosphate, NTA, and humic acid were found to accelerate the oxidation dynamics of these EDCs by Mn(VII). This was explained by the effect of in situ formed dissolved Mn(III), which could readily oxidize these EDCs but would disproportionate spontaneously without stabilizing agents.

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

Amperometric micro pH measurements in oxygenated saliva.

PubMed

Chaisiwamongkhol, Korbua; Batchelor-McAuley, Christopher; Compton, Richard G

2017-07-24

An amperometric micro pH sensor has been developed based on the chemical oxidation of carbon fibre surfaces (diameter of 9 μm and length of ca. 1 mm) to enhance the population of surface quinone groups for the measurement of salivary pH. The pH analysis utilises the electrochemically reversible two-electron, two-proton behaviour of surface quinone groups on the micro-wire electrodes. A Nernstian response is observed across the pH range 2-8 which is the pH range of many biological fluids. We highlight the measurement of pH in small volumes of biological fluids without the need for oxygen removal and specifically the micro pH electrode is examined by measuring the pH of commercial synthetic saliva and authentic human saliva samples. The results correspond well with those obtained by using commercial glass pH electrodes on large volume samples.

A new cytotoxic sesquiterpene quinone produced by Penicillium sp. F00120 isolated from a deep sea sediment sample.

PubMed

Lin, Xiuping; Zhou, Xuefeng; Wang, Fazuo; Liu, Kaisheng; Yang, Bin; Yang, Xianwen; Peng, Yan; Liu, Juan; Ren, Zhe; Liu, Yonghong

2012-01-01

A new fungal strain, displaying strong toxic activity against brine shrimp larvae, was isolated from a deep sea sediment sample collected at a depth of 1300 m. The strain, designated as F00120, was identified as a member of the genus Penicillium on the basis of morphology and ITS sequence analysis. One new sesquiterpene quinone, named penicilliumin A (1), along with two known compounds ergosterol (2) and ergosterol peroxide (3), were isolated and purified from the cultures of F00120 by silica gel column, Sephadex LH-20 column, and preparative thin layer chromatography. Their structures were elucidated by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analysis as well as comparison with literature data. The new compound penicilliumin A inhibited in vitro proliferation of mouse melanoma (B16), human melanoma (A375), and human cervical carcinoma (Hela) cell lines moderately.

Isolation and Purification of Complex II from Proteus Mirabilis Strain ATCC 29245

PubMed Central

Shabbiri, Khadija; Ahmad, Waqar; Syed, Quratulain; Adnan, Ahmad

2010-01-01

A respiratory complex was isolated from plasma membrane of pathogenic Proteus mirabilis strain ATCC 29245. It was identified as complex II consisting of succinate:quinone oxidoreductase (EC 1.3.5.1) containing single heme b. The complex II was purified by ion-exchange chromatography and gel filtration. The molecular weight of purified complex was 116.5 kDa and it was composed of three subunits with molecular weights of 19 kDa, 29 kDa and 68.5 kDa. The complex II contained 9.5 nmoles of cytochrome b per mg protein. Heme staining indicated that the 19 kDa subunit was cytochrome b. Its reduced form showed absorptions peaks at 557.0, 524.8 and 424.4 nm. The α-band was shifted from 557.0 nm to 556.8 nm in pyridine ferrohemochrome spectrum. The succinate: quinone oxidoreductase activity was found to be high in this microorganism. PMID:24031557

Photochemical electron transfer in chlorophyll-porphyrin-quinone triads. The role of the porphyrin-bridging molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.G.; Niemczyk, M.P.; Minsek, D.W.

1993-06-30

The photochemistry of four chlorophyll-porphyrin-naphthoquinone molecules possessing both fixed distances and orientations between the three components is described. These molecules consist of a methyl pyropheophorbide a or pyrochlorophyllide a that is directly bonded at its 3-position to the 5-position of a 2,8,12,18-tetraethyl-3,7,13,-17-tetramethylporphyrin, which is in turn bonded at its 15-position to a 2-triptycenenaphthoquinone. In addition, porphyrin-quinone compounds in which the chlorins are replaced by a p-tolyl group were also prepared as reference compounds. Selective metalation of the macrocycles with zinc gives the series ZCHPNQ, ZCZPNQ, HCZPNQ, HCHPNQ, HPNQ, and ZPNQ, where H, Z, C, P, and NQ denote free base,more » Zn derivative, chlorophyll, porphyrin, and naphthoquinone, respectively. Selective excitation of ZC in ZCZPNQ and ZCHPNQ, and HC in HCHPNQ dissolved in butyronitrile yields ZC[sup +]ZPNQ[sup [minus

Identification of quinone analogues as potential inhibitors of picornavirus 3C protease in vitro.

PubMed

Jung, Eunhye; Lee, Joo-Youn; Kim, Ho Jeong; Ryu, Chung-Kyu; Lee, Kee-In; Kim, Meehyein; Lee, Chong-Kyo; Go, Yun Young

2018-05-29

Picornaviruses are non-enveloped viruses that represent a large family of positive-sense single-stranded RNA viruses including a number of causative agents of many human and animal diseases such as coxsackievirus B3 (CVB3) and rhinoviruses (HRV). In this study, we performed a high-throughput screening of a compound library composed of ∼6000 small molecules in search of potential picornavirus 3C protease (3C pro ) inhibitors. As results, we identified quinone analogues that effectively inhibited both CVB3 3C pro and HRV 3C pro with IC 50 values in low micromolar range. Together with predicted binding modes of these compounds to the active site of the viral protease, it is implied that structural features of these non-peptidic inhibitors may act as useful scaffold for further anti-picornavirus drug design and development. Copyright © 2018 Elsevier Ltd. All rights reserved.

β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.

PubMed

Jeong, Moon Hee; Kim, Jin Hwan; Seo, Kang-Sik; Kwak, Tae Hwan; Park, Woo Jin

2014-11-21

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD(+)/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS. Copyright © 2014 Elsevier Inc. All rights reserved.

CrII Reactivity of Taurine/α-Ketoglutarate Dioxygenase

PubMed Central

Grzyska, Piotr K.; Hausinger, Robert P.

2008-01-01

The interaction of CrII with taurine/α-ketoglutarate (αKG) dioxygenase (TauD) was examined. CrII replaces FeII and binds stoichiometrically with αKG to the FeII/αKG-binding site of the protein, with additional CrII used to generate a chromophore attributed to a CrIII-semiquinone in a small percentage of the sample. Formation of the latter oxygen -sensitive species requires the dihydroxyphenylalanine (DOPA) quinone form of Tyr-73. This pre-formed side chain is generated by intracellular self-hydroxylation of Tyr-73 to form DOPA, which is subsequently oxidized to the quinone. No chromophore is generated when using NaBH4-treated sample, protein isolated from anaerobically grown cells, inactive TauD variants that are incapable of self-hydroxylation, or the Y73F active mutant of TauD. A CrIII-DOPA semiquinone also was observed in the herbicide hydroxylase SdpA. PMID:17973473

Cr(II) reactivity of taurine/alpha-ketoglutarate dioxygenase.

PubMed

Grzyska, Piotr K; Hausinger, Robert P

2007-11-26

The interaction of CrII with taurine/alpha-ketoglutarate (alphaKG) dioxygenase (TauD) was examined. CrII replaces FeII and binds stoichiometrically with alphaKG to the FeII/alphaKG binding site of the protein, with additional CrII used to generate a chromophore attributed to a CrIII-semiquinone in a small percentage of the sample. Formation of the latter oxygen-sensitive species requires the dihydroxyphenylalanine (DOPA) quinone form of Tyr-73. This preformed side chain is generated by intracellular self-hydroxylation of Tyr-73 to form DOPA, which is subsequently oxidized to the quinone. No chromophore is generated when using NaBH4-treated sample, protein isolated from anaerobically grown cells, inactive TauD variants that are incapable of self-hydroxylation, or the Y73F active mutant of TauD. A CrIII-DOPA semiquinone also was observed in the herbicide hydroxylase SdpA.

Searching phase II enzymes inducers, from Michael acceptor-[1,2]dithiolethione hybrids, as cancer chemopreventive agents.

PubMed

Couto, Marcos; de Ovalle, Stefani; Cabrera, Mauricio; Cerecetto, Hugo; González, Mercedes

2015-01-01

Cancer chemoprevention involves the carcinogenic process prevention, delay or reverse by the administration of chemopreventive agents, which are able to suppress or block the carcinogen metabolic activation/formation. The increased activity of phase II detoxification enzymes such as quinone-reductase (QR) and glutation-S-transferase (GST) correlates with the protection against chemically-induced carcinogenesis. It has been shown that synthetic chalcones and 3H-[1,2]-dithiole-3-thiones promote expression of genes involved in chemoprevention. Herein, the induction of phase II enzymes by designed Michael acceptor-dithiolethione hybrids was studied. Hybrids 5 and 7 displayed the induction of quinone-reductase and glutation-S-transferase in vitro in the same order on the wild-type mouse-hepatoma Hepa 1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BPrc1 cells indicating that 7 displays the best chemopreventive potential.

The Role of Glycine Residues 140 and 141 of Subunit B in the Functional Ubiquinone Binding Site of the Na+-pumping NADH:quinone Oxidoreductase from Vibrio cholerae*

PubMed Central

Juárez, Oscar; Neehaul, Yashvin; Turk, Erin; Chahboun, Najat; DeMicco, Jessica M.; Hellwig, Petra; Barquera, Blanca

2012-01-01

The Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) is the main entrance for electrons into the respiratory chain of many marine and pathogenic bacteria. The enzyme accepts electrons from NADH and donates them to ubiquinone, and the free energy released by this redox reaction is used to create an electrochemical gradient of sodium across the cell membrane. Here we report the role of glycine 140 and glycine 141 of the NqrB subunit in the functional binding of ubiquinone. Mutations at these residues altered the affinity of the enzyme for ubiquinol. Moreover, mutations in residue NqrB-G140 almost completely abolished the electron transfer to ubiquinone. Thus, NqrB-G140 and -G141 are critical for the binding and reaction of Na+-NQR with its electron acceptor, ubiquinone. PMID:22645140

Structure of a bacterial homologue of vitamin K epoxide reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Weikai; Schulman, Sol; Dutton, Rachel J.

Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain {gamma}-carboxylation of many blood coagulation factors. Here, we report the 3.6 {angstrom} crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins tomore » reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.« less

[Induction of NAD(P)H: quinone reductase by anticarcinogenic ingredients of tea].

PubMed

Qi, L; Han, C

1998-09-30

By assaying the activity of NAD(P)H: quinone reductase (QR) in Hep G2 cells exposed to inducing agents, a variety of ingredients in tea, we compared their abilities on inducing QR and preventing cancer. The results showed that tea polyphenols, tea pigments and mixed tea were all able to induce the activity of QR significantly. The single-component ingredients of tea polyphenols and tea pigments, including thearubigens, EGCG and ECG, also enhanced the activity of QR. But EGC, EC, theaflavins, tea polysaccharide and tea caffeine, showed no apparent induction of QR. We found that among those tea ingredients studied, the multi-component ingredients were more effective than the single-component ones. So we thought that the abilities of antioxidation and cancer prevention of tea depended on the combined effects of several kinds of active ingredients, which mainly include tea polyphenols and tea pigments.

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 O 2 as their only co-substrate and produce H 2O 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 toolsmore » 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.« less

Kibdelones: novel anticancer polyketides from a rare Australian actinomycete.

PubMed

Ratnayake, Ranjala; Lacey, Ernest; Tennant, Shaun; Gill, Jennifer H; Capon, Robert J

2007-01-01

The kibdelones are a novel family of bioactive heterocyclic polyketides produced by a rare soil actinomycete, Kibdelosporangium sp. (MST-108465). Complete relative stereostructures were assigned to kibdelones A-C (1-3), kibdelone B rhamnoside (5), 13-oxokibdelone A (7), and 25-methoxy-24-oxokibdelone C (8) on the basis of detailed spectroscopic analysis and chemical interconversion, as well as mechanistic and biosynthetic considerations. Under mild conditions, kibdelones B (2) and C (3) undergo a facile equilibration to kibdelones A-C (1-3), while kibdelone B rhamnoside (5) equilibrates to a mixture of kibdelone A-C rhamnosides (4-6). A plausible mechanism for this equilibration is proposed and involves air oxidation, quinone/hydroquinone redox transformations, and a choreographed sequence of keto/enol tautomerizations that aromatize ring C via a quinone methide intermediate. Kibdelones exhibit potent and selective cytotoxicity against a panel of human tumor cell lines and display significant antibacterial and nematocidal activity.

Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.

PubMed

Herrera-Mundo, Nieves; Sitges, María

2013-01-01

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Exploring the energy landscape for Q(A)(-) to Q(B) electron transfer in bacterial photosynthetic reaction centers: effect of substrate position and tail length on the conformational gating step.

PubMed

Xu, Qiang; Baciou, Laura; Sebban, Pierre; Gunner, M R

2002-08-06

The ability to initiate reactions with a flash of light and to monitor reactions over a wide temperature range allows detailed analysis of reaction mechanisms in photosynthetic reaction centers (RCs) of purple bacteria. In this protein, the electron transfer from the reduced primary quinone (Q(A)(-)) to the secondary quinone (Q(B)) is rate-limited by conformational changes rather than electron tunneling. Q(B) movement from a distal to a proximal site has been proposed to be the rate-limiting change. The importance of quinone motion was examined by shortening the Q(B) tail from 50 to 5 carbons. No change in rate was found from 100 to 300 K. The temperature dependence of the rate was also measured in three L209 proline mutants. Under conditions where Q(B) is in the distal site in wild-type RCs, it is trapped in the proximal site in the Tyr L209 mutant [Kuglstatter, A., et al. (2001) Biochemistry 40, 4253-4260]. The electron transfer slows at low temperature for all three mutants as it does in wild-type protein, indicating that conformational changes still limit the reaction rate. Thus, Q(B) movement is unlikely to be the sole, rate-limiting conformational gating step. The temperature dependence of the reaction in the L209 mutants differs somewhat from wild-type RCs. Entropy-enthalpy compensation reduces the difference in rates and free energy changes at room temperature.

Acid residues in the transmembrane helices of the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) from Vibrio cholerae involved in sodium translocation†

PubMed Central

Juárez, Oscar; Athearn, Kathleen; Gillespie, Portia; Barquera, Blanca

2009-01-01

Vibrio cholerae and many other marine and pathogenic bacteria posses a unique respiratory complex, the Na+-pumping NADH: quinone oxidoreductase (Na+-NQR)1, which pumps Na+ across the cell membrane using the energy released by the redox reaction between NADH and ubiquinone. In order to function as a selective sodium pump, Na+-NQR must contain structures that: 1) allow the sodium ion to pass through the hydrophobic core of the membrane, and 2) provide cation specificity to the translocation system. In other sodium transporting proteins, the structures that carry out these roles frequently include aspartate and glutamate residues. The negative charge of these residues facilitates binding and translocation of sodium. In this study we have analyzed mutants of acid residues located in the transmembrane helices of subunits B, D and E of Na+-NQR. The results are consistent with the participation of seven of these residues in the translocation process of sodium. Mutations at NqrB-D397, NqrD-D133 and NqrE-E95 produced a decrease of approximately ten times or more in the apparent affinity of the enzyme for sodium (Kmapp), which suggests that these residues may form part of a sodium-binding site. Mutation at other residues, including NqrB-E28, NqrB-E144, NqrB-E346 and NqrD-D88, had a large effect on the quinone reductase activity of the enzyme and its sodium sensitivity, but less effect on the apparent sodium affinity, consistent with a possible role in sodium conductance pathways. PMID:19694431

In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro.

PubMed

de Haan, Laura H J; Pot, Gerda K; Aarts, Jac M M J G; Rietjens, Ivonne M C M; Alink, Gerrit M

2006-08-01

NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose-response curve revealing a 'lower protection threshold' of 0.5mumol DCPIP/min/mg protein and an 'upper protection threshold' at 1mumol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I(3)C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed 'lower protection threshold' in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this 'lower protection threshold' will require 5-20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds.

Influence of azo dye concentration on activated sludge bacterial community in the presence of functionalized polyurethane foam.

PubMed

Lu, Hong; Wang, Jing; Lu, Shuilong; Wang, Ying; Liu, Guangfei; Zhou, Jiti; Quan, Zhexue

2015-03-01

Immobilized quinones exhibit good catalytic performance in the biodecolorization of azo dyes. However, in practical activated sludge systems, little is known about the effect of azo dye concentration on microbial communities in the presence of immobilized quinones. 454 Pyrosequencing was used to investigate structural changes and to determine the key microorganisms involved in Reactive Red X-3B decolorization in the presence of anthraquinone-2-sulfonate immobilized on polyurethane foam (AQS-PUF). Our results show that the AQS-PUF-supplemented system exhibited better stability and decolorization performance during a 30-day run than polyurethane-foam-only (PUF-supplemented) and control systems. Analysis of pyrosequencing data showed that the AQS-PUF-supplemented system had the highest bacterial diversity, followed by the control and PUF-supplemented systems during decolorization. Reactive Red X-3B and AQS-PUF significantly influenced bacterial communities at the class level: Erysipelotrichia and the most dominant Deltaproteobacteria showed significant positive correlations with Reactive Red X-3B, while unclassified Firmicutes were found to be significantly correlated with AQS-PUF. At the genus level, Desulfomicrobium, which represents 8-44 % of the total population, displayed a significant positive correlation with Reactive Red X-3B. Some bacteria, including Desulfovibrio, Shewanella, and Clostridium with relative abundances of less than 6 %, were positively correlated with AQS-PUF. These findings provide a novel insight into the changes that occur in the bacterial community during immobilized AQS-mediated decolorization. Less abundant quinone-reducing bacteria play important roles in accelerating the effect of AQS-PUF on biodecolorization.

Dithiothreitol activity by particulate oxidizers of SOA produced from photooxidation of hydrocarbons under varied NOx levels

NASA Astrophysics Data System (ADS)

Jiang, Huanhuan; Jang, Myoseon; Yu, Zechen

2017-08-01

When hydrocarbons (HCs) are atmospherically oxidized, they form particulate oxidizers, including quinones, organic hydroperoxides, and peroxyacyl nitrates (PANs). These particulate oxidizers can modify cellular materials (e.g., proteins and enzymes) and adversely modulate cell functions. In this study, the contribution of particulate oxidizers in secondary organic aerosols (SOAs) to the oxidative potential was investigated. SOAs were generated from the photooxidation of toluene, 1,3,5-trimethylbenzene, isoprene, and α-pinene under varied NOx levels. Oxidative potential was determined from the typical mass-normalized consumption rate (reaction time t = 30 min) of dithiothreitol (DTTt), a surrogate for biological reducing agents. Under high-NOx conditions, the DTTt of toluene SOA was 2-5 times higher than that of the other types of SOA. Isoprene DTTt significantly decreased with increasing NOx (up to 69 % reduction by changing the HC / NOx ratio from 30 to 5). The DTTt of 1,3,5-trimethylbenzene and α-pinene SOA was insensitive to NOx under the experimental conditions of this study. The significance of quinones to the oxidative potential of SOA was tested through the enhancement of DTT consumption in the presence of 2,4-dimethylimidazole, a co-catalyst for the redox cycling of quinones; however, no significant effect of 2,4-dimethylimidazole on modulation of DTT consumption was observed for all SOA, suggesting that a negligible amount of quinones was present in the SOA of this study. For toluene and isoprene, mass-normalized DTT consumption (DTTm) was determined over an extended period of reaction time (t = 2 h) to quantify their maximum capacity to consume DTT. The total quantities of PANs and organic hydroperoxides in toluene SOA and isoprene SOA were also measured using the Griess assay and the 4-nitrophenylboronic acid assay, respectively. Under the NOx conditions (HC / NOx ratio: 5-36 ppbC ppb-1) applied in this study, the amount of organic hydroperoxides was substantial, while PANs were found to be insignificant for both SOAs. Isoprene DTTm was almost exclusively attributable to organic hydroperoxides, while toluene DTTm was partially attributable to organic hydroperoxides. The DTT assay results of the model compound study suggested that electron-deficient alkenes, which are abundant in toluene SOA, could also modulate DTTm.

Polyphenolic reductants in cane sugar

USDA-ARS?s Scientific Manuscript database

Limited information is available to understand the chemical structure of cane sugar extracts responsible for the redox reactivity. This study employed Fremy’s salt to test the hypothesis that hydroquinone/catechol-semiquinone-quinone redox cycle is responsible for the antioxidant activity of sugarc...

Biosynthesis of hydroxycinnamoyl esters and amides in legume species

USDA-ARS?s Scientific Manuscript database

In forage crops, protein that is degraded following harvest is poorly utilized by ruminant animals, resulting in both economic and environmental consequences. In red clover, secondary reactions of quinones resulting from polyphenol oxidase (PPO)-mediated oxidation of the caffeic acid derivatives pha...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Felipe, K.B.; Benites, J.; Glorieux, C.

Highlights: •Phenylaminonaphthoquinones are redox cyclers able to form ROS. •Phenylaminonaphthoquinones plus ascorbate inhibit T24 cell growth. •Phenylaminonaphthoquinones plus ascorbate lead to necrotic-like cell death. •Phenylaminonaphthoquinones plus ascorbate impair cell cycle and affect MAPKs. •Phenylaminonaphthoquinones plus ascorbate induce a senescent cancer cell phenotype. -- Abstract: Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 andmore » Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.« less

Tannins in plant-herbivore interactions.

PubMed

Barbehenn, Raymond V; Peter Constabel, C

2011-09-01

Tannins are the most abundant secondary metabolites made by plants, commonly ranging from 5% to 10% dry weight of tree leaves. Tannins can defend leaves against insect herbivores by deterrence and/or toxicity. Contrary to early theories, tannins have no effect on protein digestion in insect herbivores. By contrast, in vertebrate herbivores tannins can decrease protein digestion. Tannins are especially prone to oxidize in insects with high pH guts, forming semiquinone radicals and quinones, as well as other reactive oxygen species. Tannin toxicity in insects is thought to result from the production of high levels of reactive oxygen species. Tannin structure has an important effect on biochemical activity. Ellagitannins oxidize much more readily than do gallotannins, which are more oxidatively active than most condensed tannins. The ability of insects to tolerate ingested tannins comes from a variety of biochemical and physical defenses in their guts, including surfactants, high pH, antioxidants, and a protective peritrophic envelope that lines the midgut. Most work on the ecological roles of tannins has been correlative, e.g., searching for negative associations between tannins and insect performance. A greater emphasis on manipulative experiments that control tannin levels is required to make further progress on the defensive functions of tannins. Recent advances in the use of molecular methods has permitted the production of tannin-overproducing transgenic plants and a better understanding of tannin biosynthetic pathways. Many research areas remain in need of further work, including the effects of different tannin types on different types of insects (e.g., caterpillars, grasshoppers, sap-sucking insects). Copyright © 2011 Elsevier Ltd. All rights reserved.

Naphthalene SOA: redox activity and naphthoquinone gas-particle partitioning

NASA Astrophysics Data System (ADS)

McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

2013-10-01

Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox-active, consuming DTT at an average rate of 118 ± 14 pmol per minute per μg of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. These results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 μg-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. Also, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

Phenoloxidase-mediated interactions of phenols and anilines with humic materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dec, J.; Bollag, J.M.

Phenoloxidases present in terrestrial systems may contribute to the formation of humus through random coupling of a variety of aromatic compounds, including xenobiotic chemicals. Because of their structural similarity to natural substrates originating mainly from lignin decomposition, xenobiotic phenols and anilines can be readily incorporated into the soil organic matter, a phenomenon referred to as binding. The underlying mechanism of binding involves oxidation of the xenobiotic substrates to free radicals or quinone products that subsequently couple directly to humus or to naturally occurring phenols that also are subject to oxidation. The oxidation can be mediated by soil phenoloxidases as wellmore » as by abiotic catalysts. The ability of the enzymes to mediate the oxidation was demonstrated in a number of model studies, in which selected pollutants were incubated with humic monomers or natural humic acids in the presence of different phenoloxidases (laccase, peroxidase, tyrosinase). Analysis of the formed complexes by mass spectrometry and {sup 13}C nuclear magnetic resonance (NMR) spectroscopy left no doubt about the formation of covalent bonds between the pollutants and humic materials. Some bonds were formed at the chlorinated sites, leading to partial dehalogenation of the aromatic contaminants. Experimental data indicated that bound phenols and anilines were unlikely to adversely affect the environment; their release from humic complexes by soil microorganisms was very limited and once released, they were subjected to mineralization. For those reasons, phenoloxidases, which proved capable of mediating the underlying reaction, are currently considered as a tool for enhancing immobilization phenomena in soil.« less

Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism

PubMed Central

Mazet, Muriel; Perozzo, Remo; Bergamini, Christian; Prati, Federica; Fato, Romana; Lenaz, Giorgio; Capranico, Giovanni; Brun, Reto; Bakker, Barbara M.; Michels, Paul A. M.; Scapozza, Leonardo; Bolognesi, Maria Laura; Cavalli, Andrea

2013-01-01

Background and Methodology Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED50 of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. Principal Findings A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC50 values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. Conclusions and Significance Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands. PMID:23350008

Acceleration of pro-caspase-3 maturation and cell migration inhibition in human breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts

PubMed Central

Naveen Kumar, D.R.; George, V. Cijo; Suresh, P.K.; Kumar, R. Ashok

2013-01-01

The aggressive nature of estrogen receptor (ER)-negative breast cancer subtype obligates for innovative targeted therapies. The present study aimed to investigate the phytoconstituents and specific anticancer activities of Rheum emodi rhizome, a known food source used locally to treat various ailments. Petroleum ether extracts (hot [PHR] and cold [PCR]) of R. emodi, exhibited significant free radical scavenging potentials through DPPH and reducing power assays, rendering them as good sources of antioxidants. The extracts, PHR and PCR had shown significant (P < 0.05) cancer-cell-specific cytotoxicity in the assayed cells (MDA-MB-231 [breast carcinoma] and WRL-68 [non-tumoral]) at 100 μg/ml, and 50 and 100 μg/ml concentrations respectively. Extracts also induced fervent apoptosis in ER-negative cells (MDA-MB-231) compared to ER-positive subtype (MCF-7), and found to involve CPP32/caspase-3 in its apoptosis induction mechanism. Moreover, extracts had an inevitable potential to inhibit the migration of metastatic breast cancer cells (MDA-MB-231) in vitro. Further, the active principles of extracts were identified through HPLC and GC-MS analysis to reveal major polyphenolics, 4,7-Dimethyl-(octahydro)indolo[4,3-fg]quinolin-10-one, 5-Oxo-isolongifolene, Valencene-2, and other quinone, quinoline and anthraquinone derivatives. The extracts are thus good candidates to target malignant ER-negative breast cancer, and the identified phytoconstituents could be eluted in further exploratory studies for use in dietary-based anti-breast cancer therapies. PMID:26417238

An Inexpensive Aqueous Flow Battery for Large-Scale Electrical Energy Storage Based on Water-Soluble Organic Redox Couples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, B; Hoober-Burkhardt, L; Wang, F

We introduce a novel Organic Redox Flow Battery (ORBAT), for Meeting the demanding requirements of cost, eco-friendliness, and durability for large-scale energy storage. ORBAT employs two different water-soluble organic redox couples on the positive and negative side of a flow battery. Redox couples such as quinones are particularly attractive for this application. No precious metal catalyst is needed because of the fast proton-coupled electron transfer processes. Furthermore, in acid media, the quinones exhibit good chemical stability. These properties render quinone-based redox couples very attractive for high-efficiency metal-free rechargeable batteries. We demonstrate the rechargeability of ORBAT with anthraquinone-2-sulfonic acid or anthraquinone-2,6-disulfonicmore » acid on the negative side, and 1,2-dihydrobenzoquinone- 3,5-disulfonic acid on the positive side. The ORBAT cell uses a membrane-electrode assembly configuration similar to that used in polymer electrolyte fuel cells. Such a battery can be charged and discharged multiple times at high faradaic efficiency without any noticeable degradation of performance. We show that solubility and mass transport properties of the reactants and products are paramount to achieving high current densities and high efficiency. The ORBAT configuration presents a unique opportunity for developing an inexpensive and sustainable metal-free rechargeable battery for large-scale electrical energy storage. (C) The Author(s) 2014. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (CC BY, http://creativecommons.orgilicenses/by/4.0/), which permits unrestricted reuse of the work in any medium, provided the original work is properly cited. All rights reserved.« less

Duroquinone reduction during passage through the pulmonary circulation.

PubMed

Audi, Said H; Bongard, Robert D; Dawson, Christopher A; Siegel, David; Roerig, David L; Merker, Marilyn P

2003-11-01

The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redox-active compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [duroquinone (DQ)] as a model amphipathic quinone reductase substrate. We measured DQ and durohydroquinone (DQH2) concentrations in the lung venous effluent after injecting, or while infusing, DQ or DQH2 into the pulmonary arterial inflow. The maximum net rates of DQ reduction to DQH2 in the rat and mouse lungs were approximately 4.9 and 2.5 micromol. min(-1).g dry lung wt(-1), respectively. The net rate was apparently the result of freely permeating access of DQ and DQH2 to tissue sites of redox reactions, dominated by dicumarol-sensitive DQ reduction to DQH2 and cyanide-sensitive DQH2 reoxidation back to DQ. The dicumarol sensitivity along with immunodetectable expression of NAD(P)H-quinone oxidoreductase 1 (NQO1) in the rat lung tissue suggest cytoplasmic NQO1 as the dominant site of DQ reduction. The effect of cyanide on DQH2 oxidation suggests that the dominant site of oxidation is complex III of the mitochondrial electron transport chain. If one envisions DQ as a model compound for examining the disposition of amphipathic NQO1 substrates in the lungs, the results are consistent with a role for lung NQO1 in determining the redox status of such compounds in the circulation. For DQ, the effect is conversion of a redox-cycling, oxygen-activating quinone into a stable hydroquinone.

Callitriche cophocarpa (water starwort) proteome under chromate stress: evidence for induction of a quinone reductase.

PubMed

Kaszycki, Paweł; Dubicka-Lisowska, Aleksandra; Augustynowicz, Joanna; Piwowarczyk, Barbara; Wesołowski, Wojciech

2018-03-01

Chromate-induced physiological stress in a water-submerged macrophyte Callitriche cophocarpa Sendtn. (water starwort) was tested at the proteomic level. The oxidative stress status of the plant treated with 1 mM Cr(VI) for 3 days revealed stimulation of peroxidases whereas catalase and superoxide dismutase activities were similar to the control levels. Employing two-dimensional electrophoresis, comparative proteomics enabled to detect five differentiating proteins subjected to identification with mass spectrometry followed by an NCBI database search. Cr(VI) incubation led to induction of light harvesting chlorophyll a/b binding protein with a concomitant decrease of accumulation of ribulose bisphosphate carboxylase (RuBisCO). The main finding was, however, the identification of an NAD(P)H-dependent dehydrogenase FQR1, detectable only in Cr(VI)-treated plants. The FQR1 flavoenzyme is known to be responsive to oxidative stress and to act as a detoxification protein by protecting the cells against oxidative damage. It exhibits the in vitro quinone reductase activity and is capable of catalyzing two-electron transfer from NAD(P)H to several substrates, presumably including Cr(VI). The enhanced accumulation of FQR1 was chromate-specific since other stressful conditions, such as salt, temperature, and oxidative stresses, all failed to induce the protein. Zymographic analysis of chromate-treated Callitriche shoots showed a novel enzymatic protein band whose activity was attributed to the newly identified enzyme. We suggest that Cr(VI) phytoremediation with C. cophocarpa can be promoted by chromate reductase activity produced by the induced quinone oxidoreductase which might take part in Cr(VI) → Cr(III) bioreduction process and thus enable the plant to cope with the chromate-generated oxidative stress.

Reengineered glucose oxidase for amperometric glucose determination in diabetes analytics.

PubMed

Arango Gutierrez, Erik; Mundhada, Hemanshu; Meier, Thomas; Duefel, Hartmut; Bocola, Marco; Schwaneberg, Ulrich

2013-12-15

Glucose oxidase is an oxidoreductase exhibiting a high β-D-glucose specificity and high stability which renders glucose oxidase well-suited for applications in diabetes care. Nevertheless, GOx activity is highly oxygen dependent which can lead to inaccuracies in amperometric β-D-glucose determinations. Therefore a directed evolution campaign with two rounds of random mutagenesis (SeSaM followed by epPCR), site saturation mutagenesis studies on individual positions, and one simultaneous site saturation library (OmniChange; 4 positions) was performed. A diabetes care well suited mediator (quinone diimine) was selected and the GOx variant (T30V I94V) served as starting point. For directed GOx evolution a microtiter plate detection system based on the quinone diimine mediator was developed and the well-known ABTS-assay was applied in microtiter plate format to validate oxygen independency of improved GOx variants. Two iterative rounds of random diversity generation and screening yielded to two subsets of amino acid positions which mainly improved activity (A173, A332) and oxygen independency (F414, V560). Simultaneous site saturation of all four positions with a reduced subset of amino acids using the OmniChange method yielded finally variant V7 with a 37-fold decreased oxygen dependency (mediator activity: 7.4 U/mg WT, 47.5 U/mg V7; oxygen activity: 172.3 U/mg WT, 30.1 U/mg V7). V7 is still highly β-D-glucose specific, highly active with the quinone diimine mediator and thermal resistance is retained (prerequisite for GOx coating of diabetes test stripes). The latter properties and V7's oxygen insensitivity make V7 a very promising candidate to replace standard GOx in diabetes care applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Bioactivation of the Cancer Chemopreventive Agent Tamoxifen to Quinone Methides by Cytochrome P4502B6 and Identification of the Modified Residue on the Apoprotein

PubMed Central

Sridar, Chitra; D'Agostino, Jaime

2012-01-01

The nonsteroidal antiestrogen tamoxifen was introduced as a treatment for breast cancer 3 decades ago. It has also been approved as a chemopreventive agent and is prescribed to women at high risk for this disease. However, several studies have shown that use of tamoxifen leads to increased risk of endometrial cancer in humans. One potential pathway of tamoxifen toxicity could involve metabolism via hydroxylation to give 4-hydroxytamoxifen (4OHtam), which may be further oxidized to form a quinone methide. CYP2B6 is a highly polymorphic drug-metabolizing enzyme, and it metabolizes a number of clinically important drugs. Earlier studies from our laboratory have shown that tamoxifen is a mechanism-based inactivator of CYP2B6. The aim of the current study was to investigate the possible formation of reactive intermediates through detection of protein covalent binding and glutathione ethyl ester adduct (GSHEE) formation. The incubation of tamoxifen with 2B6 gave rise to an adduct of 4OHtam with glutathione, which was characterized as the 4OHtam quinone methide + GSHEE with an m/z value of 719, and the structure was characterized by liquid chromatography-tandem mass spectrometry. The metabolic activation of tamoxifen in the CYP2B6 reconstituted system also resulted in the formation of an adduct to the P4502B6 apoprotein, which was identified using liquid chromatography mass spectrometry. The site responsible for the inactivation of CYP2B6 was determined by proteolytic digestion and identification of the labeled peptide. This revealed a tryptic peptide 188FHYQDQE194 with the site of adduct formation localized to Gln193 as the site modified by the reactive metabolite formed during tamoxifen metabolism. PMID:22942317

Effect of phytotoxic secondary metabolites and semisynthetic compounds from endophytic fungus Xylaria feejeensis strain SM3e-1b on spinach chloroplast photosynthesis.

PubMed

Macías-Rubalcava, Martha Lydia; García-Méndez, Marbella Claudia; King-Díaz, Beatriz; Macías-Ruvalcaba, Norma Angélica

2017-01-01

We investigated the mechanism of action on the photosynthesis light reactions of three major secondary metabolites produced by the endophytic fungus Xylaria feejeensis strain SM3e-1b, isolated from Sapium macrocarpum; and four novel derivatives of coriloxine, a major compound produced by X. feejeensis. The natural phytotoxins include one epoxycyclohexenone derivative, coriloxine (1), and two quinone derivatives (2-3). The semisynthetic derivatives of coriloxine are two cyclohexenone (4-6) and two quinone compounds (5-7). Cyclohexenone (4), (4R,5S,6R)-6-chloro-4,5-dihydroxy-3-methoxy-5-methylcyclohex-2-enone, inhibited ATP synthesis in freshly lysed spinach chloroplasts from water to MV; it also partly inhibited the basal and uncoupled photosynthetic electron transport, and significantly enhanced the phosphorylating electron transport and Mg 2+ -ATPase activity, thus demonstrating its action as an uncoupler agent. On the other hand, quinone (7), 2-((4-butylphenyl)amino)-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione, inhibited ATP synthesis, and non-cyclic electron transport from water to MV in basal, phosphorylating and uncoupled conditions in a concentration-dependent manner. Hence, (7) behaves as a Hill reaction inhibitor at the PSII electron transport on the water splitting enzyme (OEC), and on the acceptor side between P 680 and Q A . This mechanism of action was confirmed by chlorophyll a fluorescence measurements. These results indicate that coriloxine derivatives 4 and 7 could work as prototype structures for the development of new herbicides. Contrastingly, natural products 1-3, and derivatives 5 and 6 did not show a significant inhibitory effect on ATP synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Succinate dehydrogenase activity regulates PCB3-quinone-induced metabolic oxidative stress and toxicity in HaCaT human keratinocytes.

PubMed

Xiao, Wusheng; Sarsour, Ehab H; Wagner, Brett A; Doskey, Claire M; Buettner, Garry R; Domann, Frederick E; Goswami, Prabhat C

2016-02-01

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.

Higher Activities of Defense-Associated Enzymes may Contribute to Greater Resistance of Manchurian Ash to Emerald Ash Borer Than A closely Related and Susceptible Congener.

PubMed

Rigsby, Chad M; Herms, Daniel A; Bonello, Pierluigi; Cipollini, Don

2016-08-01

Emerald ash borer (EAB) is an invasive beetle native to Asia that infests and kills ash (Fraxinus spp.) in North America. Previous experiments indicated that larvae feeding on co-evolved, resistant Manchurian ash (F. mandshurica) have increased antioxidant and quinone-protective enzyme activities compared to larvae feeding on susceptible North American species. Here, we examined mechanisms of host-generated oxidative and quinone-based stress and other putative defenses in Manchurian ash and the closely related and chemically similar, but susceptible, black ash (F. nigra), with and without exogenous application of methyl jasmonate (MeJA) to induce resistance mechanisms. Peroxidase activities were 4.6-13.3 times higher in Manchurian than black ash, although both species appeared to express the same three peroxidase isozymes. Additionally, peroxidase-mediated protein cross-linking activity was stronger in Manchurian ash. Polyphenol oxidase, β-glucosidase, chitinase, and lipoxygenase activities also were greater in Manchurian ash, but only lipoxygenase activity increased with MeJA application. Phloem H 2 O 2 levels were similar and were increased by MeJA application in both species. Lastly, trypsin inhibitor activity was detected in methanol and water extracts that were not allowed to oxidize, indicating the presence of phenolic-based trypsin inhibitors. However, no proteinaceous trypsin inhibitor activity was detected in either species. In response to MeJA application, Manchurian ash had higher trypsin inhibitor activity than black ash using the unoxidized water extracts, but no treatment effects were detected using methanol extracts. Based on these results we hypothesize that peroxidases, lignin polymerization, and quinone generation contribute to the greater resistance to EAB displayed by Manchurian ash.

Cranberry extract-enriched diets increase NAD(P)H:quinone oxidoreductase and catalase activities in obese but not in nonobese mice.

PubMed

Boušová, Iva; Bártíková, Hana; Matoušková, Petra; Lněničková, Kateřina; Zappe, Lukáš; Valentová, Kateřina; Szotáková, Barbora; Martin, Jan; Skálová, Lenka

2015-10-01

Consumption of antioxidant-enriched diets is 1 method of addressing obesity, which is associated with chronic oxidative stress and changes in the activity/expression of various enzymes. In this study, we hypothesized that the modulation of antioxidant enzymes and redox status through a cranberry extract (CBE)-enriched diet would differ between obese and nonobese mice. The CBE used in this study was obtained from the American cranberry (Vaccinium macrocarpon, Ericaceae), a popular constituent of dietary supplements that is a particularly rich source of (poly)phenols and has strong antioxidant properties. The present study was designed to test and compare the in vivo effects of 28-day consumption of a CBE-enriched diet (2%) on the antioxidant status of nonobese mice and mice with monosodium glutamate-induced obesity. Plasma, erythrocytes, liver, and small intestine were studied concurrently to obtain more complex information. The specific activities, protein, and messenger RNA expression levels of antioxidant enzymes as well as the levels of malondialdehyde and thiol (SH) groups were analyzed. Cranberry extract treatment increased the SH group content in plasma and the glutathione S-transferase activity in the erythrocytes of the obese and nonobese mice. In addition, in the obese animals, the CBE treatment reduced the malondialdehyde content in erythrocytes and increased quinone oxidoreductase (liver) and catalase (erythrocytes and small intestine) activities. The elevation of hepatic quinone oxidoreductase activity was accompanied by an increase in the corresponding messenger RNA levels. The effects of CBE on the activity of antioxidant enzymes and redox status were more pronounced in the obese mice compared with the nonobese mice. Copyright © 2015 Elsevier Inc. All rights reserved.

A cannabinoid anticancer quinone, HU-331, is more potent and less cardiotoxic than doxorubicin: a comparative in vivo study.

PubMed

Kogan, Natalya M; Schlesinger, Michael; Peters, Maximilian; Marincheva, Gergana; Beeri, Ronen; Mechoulam, Raphael

2007-08-01

Several quinones have been found to be effective in the treatment of some forms of cancer; however, their cumulative heart toxicity limits their use. The cannabinoid quinone HU-331 [3S,4R-p-benzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl] is highly effective against tumor xenografts in nude mice. We report now a comparison of the anticancer activity of HU-331 and its cardiotoxicity with those of doxorubicin in vivo. General toxicity was assayed in Sabra, nude and SCID-NOD mice. The anticancer activity in vivo was assessed by measurement of the tumors with an external caliper in HT-29 and Raji tumor-bearing mice and by weighing the excised tumors. Left ventricular function was evaluated with transthoracic echocardiography. Myelotoxicity was evaluated by blood cell count. Cardiac troponin T (cTnT) plasma levels were determined by immunoassay. HU-331 was found to be much less cardiotoxic than doxorubicin. The control and the HU-331-treated groups gained weight, whereas the doxorubicin-treated group lost weight during the study. In HT-29 colon carcinoma, the tumor weight in the HU-331-treated group was 54% smaller than in the control group and 30% smaller than in the doxorubicin-treated group. In Raji lymphoma, the tumor weight in the HU-331-treated group was 65% smaller than in the control group and 33% smaller than in the doxorubicin-treated group. In contrast to doxorubicin, HU-331 did not generate reactive oxygen species in mice hearts (measured by protein carbonylation levels and malondialdehyde levels). In vivo, HU-331 was more active and less toxic than doxorubicin and thus it has a high potential for development as a new anticancer drug.

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.

Roles of the Sodium-Translocating NADH:Quinone Oxidoreductase (Na+-NQR) on Vibrio cholerae Metabolism, Motility and Osmotic Stress Resistance

PubMed Central

Minato, Yusuke; Halang, Petra; Quinn, Matthew J.; Faulkner, Wyatt J.; Aagesen, Alisha M.; Steuber, Julia; Stevens, Jan F.; Häse, Claudia C.

2014-01-01

The Na+ translocating NADH:quinone oxidoreductase (Na+-NQR) is a unique respiratory enzyme catalyzing the electron transfer from NADH to quinone coupled with the translocation of sodium ions across the membrane. Typically, Vibrio spp., including Vibrio cholerae, have this enzyme but lack the proton-pumping NADH:ubiquinone oxidoreductase (Complex I). Thus, Na+-NQR should significantly contribute to multiple aspects of V. cholerae physiology; however, no detailed characterization of this aspect has been reported so far. In this study, we broadly investigated the effects of loss of Na+-NQR on V. cholerae physiology by using Phenotype Microarray (Biolog), transcriptome and metabolomics analyses. We found that the V. cholerae ΔnqrA-F mutant showed multiple defects in metabolism detected by Phenotype Microarray. Transcriptome analysis revealed that the V. cholerae ΔnqrA-F mutant up-regulates 31 genes and down-regulates 55 genes in both early and mid-growth phases. The most up-regulated genes included the cadA and cadB genes, encoding a lysine decarboxylase and a lysine/cadaverine antiporter, respectively. Increased CadAB activity was further suggested by the metabolomics analysis. The down-regulated genes include sialic acid catabolism genes. Metabolomic analysis also suggested increased reductive pathway of TCA cycle and decreased purine metabolism in the V. cholerae ΔnqrA-F mutant. Lack of Na+-NQR did not affect any of the Na+ pumping-related phenotypes of V. cholerae suggesting that other secondary Na+ pump(s) can compensate for Na+ pumping activity of Na+-NQR. Overall, our study provides important insights into the contribution of Na+-NQR to V. cholerae physiology. PMID:24811312

Acetate in mixotrophic growth medium affects photosystem II in Chlamydomonas reinhardtii and protects against photoinhibition.

PubMed

Roach, Thomas; Sedoud, Arezki; Krieger-Liszkay, Anja

2013-10-01

Chlamydomonas reinhardtii is a photoautotrophic green alga, which can be grown mixotrophically in acetate-supplemented media (Tris-acetate-phosphate). We show that acetate has a direct effect on photosystem II (PSII). As a consequence, Tris-acetate-phosphate-grown mixotrophic C. reinhardtii cultures are less susceptible to photoinhibition than photoautotrophic cultures when subjected to high light. Spin-trapping electron paramagnetic resonance spectroscopy showed that thylakoids from mixotrophic C. reinhardtii produced less (1)O2 than those from photoautotrophic cultures. The same was observed in vivo by measuring DanePy oxalate fluorescence quenching. Photoinhibition can be induced by the production of (1)O2 originating from charge recombination events in photosystem II, which are governed by the midpoint potentials (Em) of the quinone electron acceptors. Thermoluminescence indicated that the Em of the primary quinone acceptor (QA/QA(-)) of mixotrophic cells was stabilised while the Em of the secondary quinone acceptor (QB/QB(-)) was destabilised, therefore favouring direct non-radiative charge recombination events that do not lead to (1)O2 production. Acetate treatment of photosystem II-enriched membrane fragments from spinach led to the same thermoluminescence shifts as observed in C. reinhardtii, showing that acetate exhibits a direct effect on photosystem II independent from the metabolic state of a cell. A change in the environment of the non-heme iron of acetate-treated photosystem II particles was detected by low temperature electron paramagnetic resonance spectroscopy. We hypothesise that acetate replaces the bicarbonate associated to the non-heme iron and changes the environment of QA and QB affecting photosystem II charge recombination events and photoinhibition. Copyright © 2013 Elsevier B.V. All rights reserved.

NQO1 and CYP450 reductase decrease the systemic exposure of rifampicin-quinone and mediate its redox cycle in rats.

PubMed

Shi, Fuguo; Li, Xiaobing; Pan, Hong; Ding, Li

2017-01-05

Rifampicin (RIF) is used in regimens for infections caused by Mycobacteria accompanied by serious adverse reactions. Rifampicin-quinone (RIF-Q) is a major autoxidation product of RIF. It is not clear whether RIF-Q plays a role in RIF induced adverse reactions. Investigation of the systemic exposure of RIF-Q is helpful to better understand the role of RIF-Q in RIF induced adverse reactions. In this study, a simple and reproducible high performance liquid chromatography-mass spectrometry (LC-MS) method involving a procedure to prevent the RIF from oxidation for simultaneous quantification of RIF and RIF-Q in rat plasma has been developed and validated, and applied to elucidate the systemic exposure of RIF-Q in rats. The pharmacokinetics data showed that the systemic exposure of RIF-Q was very low (0.67% of RIF, AUC 0-24 ) in rats after oral administration of RIF. However, RIF-Q may undergo the redox cycle in vivo by the evidence that the majority of RIF-Q was reduced to RIF after an oral dose of RIF-Q. Pretreatment with the NAD(P)H: quinone oxidoreductase 1 (NQO1) specific inhibitor dicoumarol and/or cytochrome P450 reductase (CPR) inhibitor diphenyleneiodonium suppressed the redox cycle and significantly increased the systemic exposure of RIF-Q. The inhibitors also attenuated the redox cycle induced reactive oxygen species formation and cytotoxicity in RIF-Q-treated HepG2 cells. These results indicate that NQO1 and CPR play an important role in redox cycle of RIF-Q and may thus contribute to RIF-induced adverse reactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship in between Chemical Oxidation and Browning of Flavanols

NASA Astrophysics Data System (ADS)

Dong, X.; Zhang, Y. L.; Wang, F.; Pang, M. X.; Qi, J. H.

2016-08-01

Catechin, epicatechin and chlorogenic acid are widely distributed in the plant kingdom. At present, influencing factors of phenol chemical oxidation is little research. In order to study non-enzymatic browning factors, this research utilized catechin, epicatechin and chlorogenic acid to establish simulation systems. The browning degree and products of flavanols were investigated by transmittance and high-performance liquid chromatography (HPLC). The main results and conclusions were follows. The brown generation is increased after phenols of chemical oxidation at 50°C and at pH 3.7 phosphate buffered saline, the sequence of influencing factor of browning is pH > kind of phenol > temperature. Oxidation of compounds of catechin and epicatechin results in formation of their Methylene quinone or o -Quinones. In addition, oxidation products of catechin, epicatechin and chlorogenic acid were mixture of different molecular sizes. The research has showed that brown generation correlated well with chemical oxidation of phenols and chemical oxidation reaction generated larger molecular weight polymers.

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.

Pre-harvest methyl jasmonate treatment enhances cauliflower chemoprotective attributes without a loss in postharvest quality.

PubMed

Ku, Kang Mo; Choi, Jeong-Hee; Kushad, Mosbah M; Jeffery, Elizabeth H; Juvik, John A

2013-06-01

Methyl jasmonate (MeJA) treatment can significantly increase glucosinolate (GS) concentrations in Brassica vegetables and potentially enhance anticancer bioactivity. Although MeJA treatment may promote ethylene biosynthesis, which can be detrimental to postharvest quality, there are no previous reports of its effect on cauliflower postharvest quality. To address this, cauliflower curds in field plots were sprayed with either 0.1 % Triton X-100 (control) or 500 μM MeJA solutions four days prior to harvest, then stored at 4 °C. Tissue subsamples were collected after 0, 10, 20, and 30 days of postharvest storage and assayed for visual color change, ethylene production, GS concentrations, and extract quinone reductase inductive activity. MeJA treatment increased curd GS concentrations of glucoraphanin, glucobrassicin, and neoglucobrassicin by 1.5, 2.4, and 4.6-fold over controls, respectively. MeJA treated cauliflower showed significantly higher quinone reductase activity, a biomarker for anticancer bioactivity, without reducing visual color and postharvest quality for 10 days at 4 °C storage.

Correlation of quinone reductase activity and allyl isothiocyanate formation among different genotypes and grades of horseradish roots.

PubMed

Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A; Kushad, Mosbah M

2015-03-25

Horseradish (Armoracia rusticana) is a perennial crop and its ground root tissue is used in condiments because of the pungency of the glucosinolate (GS)-hydrolysis products allyl isothiocyanate (AITC) and phenethyl isothiocyanate (PEITC) derived from sinigrin and gluconasturtiin, respectively. Horseradish roots are sold in three grades: U.S. Fancy, U.S. No. 1, and U.S. No. 2 according to the USDA standards. These grading standards are primarily based on root diameter and length. There is little information on whether root grades vary in their phytochemical content or potential health promoting properties. This study measured GS, GS-hydrolysis products, potential anticancer activity (as quinone reductase inducing activity), total phenolic content, and antioxidant activities from different grades of horseradish accessions. U.S. Fancy showed significantly higher sinigrin and AITC concentrations than U.S. No. 1 ,whereas U.S. No. 1 showed significantly higher concentrations of 1-cyano 2,3-epithiopropane, the epithionitrile hydrolysis product of sinigrin, and significantly higher total phenolic concentrations than U.S. Fancy.

Allyl isothiocyanate enhances shelf life of minimally processed shredded cabbage.

PubMed

Banerjee, Aparajita; Penna, Suprasanna; Variyar, Prasad S

2015-09-15

The effect of allyl isothiocyanate (AITC), in combination with low temperature (10°C) storage on post harvest quality of minimally processed shredded cabbage was investigated. An optimum concentration of 0.05μL/mL AITC was found to be effective in maintaining the microbial and sensory quality of the product for a period of 12days. Inhibition of browning was shown to result from a down-regulation (1.4-fold) of phenylalanine ammonia lyase (PAL) gene expression and a consequent decrease in PAL enzyme activity and o-quinone content. In the untreated control samples, PAL activity increased following up-regulation in PAL gene expression that could be linearly correlated with enhanced o-quinone formation and browning. The efficacy of AITC in extending the shelf life of minimally processed shredded cabbage and its role in down-regulation of PAL gene expression resulting in browning inhibition in the product is reported here for the first time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cr(VI) remediation by enriched sediment with anthraquinone-2,6-disulfonate as electron shuttles

NASA Astrophysics Data System (ADS)

Chen, Hong; Li, Xiaojuan; Xu, Zhiwei

Hexavalent chromium (Cr(VI)) is a priority pollutant in the USA and many other countries. This study investigated the simultaneous remediation of Cr(VI) in sediment enriched with quinone-reducing microorganisms via a closely coupled, biotic-abiotic pathway. The results showed that Cr(VI) remediation was achieved by sediment adsorption and reduction of quinone-reducing microorganism. Moreover, microorganism reduction of Cr(VI) could be continued when sediment adsorption was saturated after long-term Cr(VI) remediation. The acetate and anthraquinone-2,6-disulfonate (AQDS), which acted as exogenous carbon and electron shuttle, respectively, were two crucial factors. The optimum concentrations of acetate and AQDS were 5 mM and 1 mM when the initial Cr(VI) concentration was 10 mg/L. AQDS was recycled, and it acted in a catalytic-type manner for the bacterial reduction of Cr(VI). Thus, biological humus reduction might provide an extensive pathway for the sequestration and detoxification of Cr(VI) in anaerobic soils, water, and industrial effluents.

Bisphenol A 3,4-quinone induces the conversion of xanthine dehydrogenase into oxidase in vitro.

PubMed

Sakuma, Satoru; Nakanishi, Masahiko; Morinaga, Kazuhiro; Fujitake, Mihoyo; Wada, Shun-ichi; Fujimoto, Yohko

2010-01-01

In the present study, we assessed the influence of bisphenol A (BPA) and bisphenol A 3,4-quinone (BPAQ) on the conversion of xanthine dehydrogenase (XD) into xanthine oxidase (XO) in the rat liver in vitro. BPA up to 100 micromol/L did not affect the XO and XD activities in the partially purified cytosolic fraction from rat liver, whereas BPAQ (2-10 micromol/L) dose-dependently enhanced the XO activity concomitant with a decrease in the XD activity, implying that BPAQ, but not BPA, can convert XD into the reactive oxygen species (ROS) producing the form XO. Furthermore, it was found that BPAQ could increase the generation of ROS and oxidize the guanine moiety of deoxyguanosine in the DNA of primary rat hepatocyte cultures. These results suggest that BPAQ has the potential to convert XD into XO in the liver, which in turn may lead to ROS generation and oxidative DNA damage in this region. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Biological Reactive Intermediates (BRIs) Formed from Botanical Dietary Supplements

PubMed Central

Dietz, Birgit M.; Bolton, Judy L.

2013-01-01

The use of botanical dietary supplements is increasingly popular, due to their natural origin and the perceived assumption that they are safer than prescription drugs. While most botanical dietary supplements can be considered safe, a few contain compounds, which can be converted to reactive biological reactive intermediates (BRIs) causing toxicity. For example, sassafras oil contains safrole, which can be converted to a reactive carbocation forming genotoxic DNA adducts. Alternatively, some botanical dietary supplements contain stable BRIs such as simple Michael acceptors that react with chemosensor proteins such as Keap1 resulting in induction of protective detoxification enzymes. Examples include curcumin from turmeric, xanthohumol from hops, and Z-ligustilide from dang gui. Quinones (sassafras, kava, black cohosh), quinone methides (sassafras), and epoxides (pennyroyal oil) represent BRIs of intermediate reactivity, which could generate both genotoxic and/or chemopreventive effects. The biological targets of BRIs formed from botanical dietary supplements and their resulting toxic and/or chemopreventive effects are closely linked to the reactivity of BRIs as well as dose and time of exposure. PMID:20970412

Bioorthogonal Metabolic DNA Labelling using Vinyl Thioether-Modified Thymidine and o-Quinolinone Quinone Methide.

PubMed

Gubu, Amu; Li, Long; Ning, Yan; Zhang, Xiaoyun; Lee, Seonghyun; Feng, Mengke; Li, Qiang; Lei, Xiaoguang; Jo, Kyubong; Tang, Xinjing

2018-04-17

Bioorthogonal metabolic DNA labeling with fluorochromes is a powerful strategy to visualize DNA molecules and their functions. Here, we report the development of a new DNA metabolic labeling strategy enabled by the catalyst-free bioorthogonal ligation using vinyl thioether modified thymidine and o-quinolinone quinone methide. With the newly designed vinyl thioether-modified thymidine (VTdT), we added labeling tags on cellular DNA, which could further be linked to fluorochromes in cells. Therefore, we successfully visualized the DNA localization within cells as well as single DNA molecules without other staining reagents. In addition, we further characterized this bioorthogonal DNA metabolic labeling using DNase I digestion, MS characterization of VTdT as well as VTdT-oQQF conjugate in cell nuclei or mitochondria. This technique provides a powerful strategy to study DNA in cells, which paves the way to achieve future spatiotemporal deciphering of DNA synthesis and functions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Production, purification and detergent exchange of isotopically labeled Bacillussubtilis cytochrome b₅₅₈ (SdhC).

PubMed

Baureder, Michael; Hederstedt, Lars

2011-11-01

Cytochrome b₅₅₈ of the gram-positive bacterium Bacillussubtilis is the membrane anchor subunit of the succinate:quinone oxidoreductase of the citric acid cycle. The cytochrome consists of the SdhC polypeptide (202 residues) and two protoheme IX groups that function in transmembrane electron transfer to menaquinone. The general structure of the cytochrome is known from extensive experimental studies and by comparison to Wolinellasuccinogenes fumarate reductase for which the X-ray crystal structure has been determined. Solution state NMR can potentially be used to identify the quinone binding site(s) and study, e.g. redox-linked, dynamics of cytochrome b₅₅₈. In this work we present an efficient procedure for the isolation of preparative amounts of isotopically labeled B. subtilis cytochrome b₅₅₈ produced in Escherichia coli. We have also evaluated several detergents suitable for NMR for their effectiveness in maintaining the cytochrome solubilized and intact for days at room temperature. Copyright © 2011 Elsevier Inc. All rights reserved.

Characteristics and Kinetic Analysis of AQS Transformation and Microbial Goethite Reduction:Insight into "Redox mediator-Microbe-Iron oxide" Interaction Process.

PubMed

Zhu, Weihuang; Shi, Mengran; Yu, Dan; Liu, Chongxuan; Huang, Tinglin; Wu, Fengchang

2016-03-29

The characteristics and kinetics of redox transformation of a redox mediator, anthraquinone-2-sulfonate (AQS), during microbial goethite reduction by Shewanella decolorationis S12, a dissimilatory iron reduction bacterium (DIRB), were investigated to provide insights into "redox mediator-iron oxide" interaction in the presence of DIRB. Two pre-incubation reaction systems of the "strain S12- goethite" and the "strain S12-AQS" were used to investigate the dynamics of goethite reduction and AQS redox transformation. Results show that the concentrations of goethite and redox mediator, and the inoculation cell density all affect the characteristics of microbial goethite reduction, kinetic transformation between oxidized and reduced species of the redox mediator. Both abiotic and biotic reactions and their coupling regulate the kinetic process for "Quinone-Iron" interaction in the presence of DIRB. Our results provide some new insights into the characteristics and mechanisms of interaction among "quinone-DIRB- goethite" under biotic/abiotic driven.

Inhibition of Human Vascular NADPH Oxidase by Apocynin Derived Oligophenols

PubMed Central

Mora-Pale, Mauricio; Weïwer, Michel; Yu, Jingjing; Linhardt, Robert J.; Dordick, Jonathan S.

2009-01-01

Enzymatic oxidation of apocynin, which may mimic in vivo metabolism, affords a large number of oligomers (apocynin oxidation products, AOP) that inhibit vascular NADPH oxidase. In vitro studies of NADPH oxidase activity were performed to identify active inhibitors, resulting in a trimer hydroxylated quinone (IIIHyQ) that inhibited NADPH oxidase with an IC50 = 31 nM. Apocynin itself possessed minimal inhibitory activity. NADPH oxidase is believed to be inhibited through prevention of the interaction between two NADPH oxidase subunits, p47phox and p22phox. To that end, while apocynin was unable to block the interaction of his-tagged p47phox with a surface immobilized biotinalyted p22phox peptide, the IIIHyQ product strongly interfered with this interaction (apparent IC50 = 1.6 μM). These results provide evidence that peroxidase-catalyzed AOP, which consist of oligomeric phenols and quinones, inhibit critical interactions that are involved in the assembly and activation of human vascular NADPH oxidase. PMID:19523836

PQQ: Biosynthetic studies in Methylobacterium AM1 and Hyphomicrobium X using specific TC labeling and NMR. [Pyrroloquinoline quinones

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 tomore » 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.« less

Transcriptional regulation of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase in murine hepatoma cells by 6-(methylsufinyl)hexyl isothiocyanate, an active principle of wasabi (Eutrema wasabi Maxim).

PubMed

Hou, D X; Fukuda, M; Fujii, M; Fuke, Y

2000-12-20

Wasabi is a very popular pungent spice in Japan. This study examined the ability of 6-(methylsufinyl)hexyl isothiocyanate (6-MITC), an active principle of wasabi, to induce the cellular expression of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase (QR) in Hepa 1c1c7 cells. The cells were treated with various concentrations of 6-MITC, and were then assessed for cell growth, QR activity and QR mRNA expression. The induction of QR activity and QR mRNA expression was time- and dose-responsive over a narrow range of 0.1-5 microM, with declining induction at higher concentrations due to cell toxicity. Furthermore, transfection studies demonstrated that the induction of transcription of the QR gene by 6-MITC involved an antioxidant/electrophile-responsive element (ARE/EpRE) activation. Our results suggest a novel mechanism by which dietary wasabi 6-MITC may be implicated in cancer chemoprevention.

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

Utilizing a CdTe quantum dots-enzyme hybrid system for the determination of both phenolic compounds and hydrogen peroxide.

PubMed

Yuan, Jipei; Guo, Weiwei; Wang, Erkang

2008-02-15

In this paper, we attempt to construct a simple and sensitive detection method for both phenolic compounds and hydrogen peroxide, with the successful combination of the unique property of quantum dots and the specificity of enzymatic reactions. In the presence of H2O2 and horseradish peroxidase, phenolic compounds can quench quantum dots' photoluminescence efficiently, and the extent of quenching is severalfold to more than 100-fold increase. Quinone intermediates produced from the enzymatic catalyzed oxidation of phenolic compounds were believed to play the main role in the photoluminescence quenching. Using a quantum dots-enzyme system, the detection limits for phenolic compounds and hydrogen peroxide were detected to be approximately 10(-7) mol L(-1). The coupling of efficient quenching of quantum dot photoluminescence by quinone and the effective enzymatic reactions make this a simple and sensitive method for phenolic compound detection and great potential in the development of H2O2 biosensors for various analytes.

Amine quinone polyurethane polymers for improved performance in advanced particulate media

NASA Astrophysics Data System (ADS)

Warren, G. W.; Sharma, Rahul; Nikles, D. E.; Hu, Y.; Street, S. C.

1999-03-01

The magnetic layer used in commercial, high density, metal particle recording media consists of sub-micron sized Fe particles suspended in a polyurethane polymer binder. New amine-quinone polymers, AQPU15 and AQPU100, have been developed for improving corrosion resistance of the particles. A fundamental study of the nature of the AQ polymer/metal oxide interface and its relationship to corrosion resistance is reported. Electrochemical impedance spectroscopy was used to evaluate corrosion behavior of Fe substrates coated with two different thicknesses of each polymer. The extent of corrosion of Fe particles coated with AQ polymers was also measured via the loss in MS with time of immersion in an acid solution. AQ coated particles showed significant improvement in corrosion resistance. FTIR-RA and XPS data show an interaction between AQM14A, a simple model for a portion of the polymer, and metal (Fe, Cu, Al) surfaces which occurs through the π system of the AQ functional group.

Microbial community in biofilm on membrane surface of submerged MBR: effect of in-line cleaning chemical agent.

PubMed

Lim, B R; Ahn, K H; Song, K G; Cho, J W

2005-01-01

The objective of this study was to investigate the change in microbial community pattern with the effect of cleaning agent using a quinone profile that is used for membrane in-line chemical cleaning in SMBR. The dominant quinone types of biofilm were ubiquinone (UQs)-8, -10, followed by menaquinone (MKs)-8(H4), -7 and UQ-9, but those of suspended microorganisms were UQ-8, UQ-10 followed by MKs-8(H4), -7 and -11. Both UQ and MK contents decreased with increasing NaCIO dosage and it seems that there is more resistance from UQ compared to MK. In addition, COD and DOC concentrations increased with increasing NaClO dosage up to 0.05 g-NaCIO/g-SS. The organic degradation performance of the microbial community in the presence of NaClO was impaired. The present study suggested that larger added amounts of NaClO caused an inhibition of organic degradation and cell lysis.

Phenolic derivatives from soy flour ethanol extract are potent in vitro quinone reductase (QR) inducing agents.

PubMed

Bolling, Bradley W; Parkin, Kirk L

2008-11-26

The fractionation of soy flour directed by a cellular bioassay for induction of phase 2 detoxification enzymes was used to identify quinone reductase (QR) inducing agents. A phospholipid-depleted, 80% methanol-partitioned isolate from a crude ethanol extract of soy flour was resolved using normal phase medium-pressure liquid chromatography (MPLC). Early eluting fractions were found to be the most potent QR inducing agents among the separated fractions. Fraction 2 was the most potent, doubling QR at <2 mug/mL. Further fractionation of this isolate led to the identification of several constituents. Fatty acids and sn-1 and sn-2 monoacylglycerols were identified, but were not highly potent QR inducers. Benzofuran-3-carbaldehyde, 4-hydroxybenzaldeyde, 4-ethoxybenzoic acid, 4-ethoxycinnamic acid, benzofuran-2-carboxylic ethyl ester, and ferulic acid ethyl ester (FAEE) were also identified as QR inducing constituents of this fraction. FAEE was the most potent of the identified constituents, doubling QR specific activity at 3.2 muM in the cellular bioassay.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikuno, Shota; Taguchi, Keiko; Iwamoto, Noriko

1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM{sub 2.5}. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC{sub 5} value of 18.7 {mu}M. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VR1) signaling. Additionally, 1,2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation ofmore » PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.« less

DIFFERENTIATING MECHANISMS OF REACTIVE CHEMICAL TOXICITY IN ISOLATED TROUT HEPATOCYTES

EPA Science Inventory

The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl 1,4-naphthoquinone (MNQ ),1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. Mor...

Phytochemical composition and antioxidant capacity of whole wheat products

USDA-ARS?s Scientific Manuscript database

Whole wheat contains an array of phytochemicals. We quantified alkylresorcinols (AR), phenolic acids, phytosterols, and tocols in six whole wheat products and characterized their antioxidant capacity and ability to induce quinone reductase activity (QR). Total AR content ranged from 136.8 to 233.9 m...

Cofacial Assembly of Metallomacrocycles. A Molecular Engineering Approach to Electrically Conductive Polymers.

DTIC Science & Technology

1981-05-13

34molecular metals." THE COFACIAL ASSEMBLY STRATEGY Although the above molecular macrocycle, halogen cocrystalli - zation approach to the synthesis of...substitute various oxidizing quinones for halogens in the cocrystallization synthesis have failed because integrated stacK (Figure 2C,D) insulators are

COLLECTION EFFICIENCY OF THE HIGH VOLUME SMALL SURFACE SAMPLER ON WORN CARPETS

EPA Science Inventory

Collection Efficiency of the High Volume Small Surface Sampler on Worn Carpets

Erik R. Svendsen*?, Peter S. Thorne*, Stephen J. Reynolds*?, Patrick T. O'Shaughnessy*, Alba Quinones*, Dale Zimmerman*, and Nervana Metwali*

*University of Iowa College of Public Health<...

Polymerization of Quinone-Crosslinked Marine Bioadhesive Protein

DTIC Science & Technology

1988-10-05

T. (1988) Adhesive protein of ribbed mussels: a natural glue with some features of collagen . To: J. Biol. Chem. Rzepecki, L., Nagafuchi, T. and...protein as inducing agent in the settlement of Mytilus edulis larvae", and "Hemolytic toxins of two marine jellyfish ", respectively. Tatsuhiko

Ranking mechanical pulps for their potential to photoyellow

Treesearch

Umesh P. Agarwal

2000-01-01

Recently found experimental evidence has provided strong support for an alternative photoyellowing mechanism that suggests that pulp- photoyellowing occurs due to direct photooxidation of hydroquinones (present in mechanical pulps) top-quinones. Because hydroquinones were found to be present in pulps, it may be possible to quantify them. Quantification of mechanical-...

Biodegradation of RDX by Stimulating Humic Substance- and Fe(III) - Reduction

DTIC Science & Technology

2007-06-19

Sediments with Quinones and Humus as Terminal Electron Acceptors. Appl. Environ. Microbiol. 67:4471-4478. 10. Coates, J. D., D. J. Ellis, E. L...167. 57. Stevenson, F. J. 1982. Humus chemistry genesis, composition, reactions. Wiley Interscience, New York. 58. Stolz, J. F., D. R. Lovley, and

PBT,PBO-Based Hybrid Polymers with Nonlinear Optical Properties or High Electrical Conductivity

DTIC Science & Technology

1988-08-29

standing. Experiments with stronger oxidizing agents such as nitrosonium salts (e.g., NO+Br4, NO+PF6) and high-potential quinones (e.g., DDQ...several unique possibilities. First, the ionic structure should raise Tg. Second, electrophoretic ion migration under the influence of the poling field

77 FR 51957 - Defense Federal Acquisition Regulation Supplement: Clarification of “F” Orders in the Procurement...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... multi-agency contracts, or basic ordering agreements. The proposed text also directs that a... agreements, or blanket purchase agreements. As a result of the proposed rule, new awards under the AbilityOne... Part 204 Government procurement. Manuel Quinones, Editor, Defense Acquisition Regulations System...

78 FR 30232 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

.... DATES: Effective: May 22, 2013. FOR FURTHER INFORMATION CONTACT: Mr. Manuel Quinones, Defense... MATTERS 204.1105 [Amended] 0 2. Amend section 204.1105 by removing the word ``clause'' and adding the word.... Section 252.204-7004 is amended by removing from the clause heading ``(DATE)'' and adding ``(MAY 2013...

Beyond brown: polyphenol oxidases as enzymes of plant specialized metabolism

USDA-ARS?s Scientific Manuscript database

Most cloned and/or characterized plant polyphenol oxidases (PPOs) have catecholase activity (i.e., they oxidize o-diphenols to o-quinones) and are localized or predicted to be localized to plastids. As a class, they have broad substrate specificity and are associated with browning of produce and oth...

The End of the Six-Party Talks?

DTIC Science & Technology

2007-01-01

Pyongyang is wary of Beijing’s international influence, its ability to collaborate with the United States and South Korea, its willingness to foster ...Kenneth Quinones, “ Dualism in the Bush Administration’s North Korea Policy,” Asian Perspective, XXVII, no. 1, 2003, 197-224; Karin Lee and Adam Miles

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

PubMed Central

Liu, Hua; Talalay, Paul

2013-01-01

Exemestane (6-methyleneandrosta-1,4-diene-3,17-dione) is a synthetic steroidal inhibitor of the aromatase reaction that catalyzes the terminal and rate-limiting step of the biosynthesis of estrogens. It is active clinically in preventing, delaying progression of, and treating mammary cancers, many of which are estrogen receptor-positive. A striking feature of the structure of exemestane is an extended system of conjugated Michael reaction functions, which is also characteristic of inducers of a broad network of chemoprotective genes regulated by the Keap1 (Kelch-like ECA-associated protein)/Nrf2 (nuclear factor E2-related factor 2)/ARE (antioxidant response element) signaling system. These genes are largely involved in xenobiotic metabolism and antioxidative and anti-inflammatory protection, as well as the synthesis and reduction of glutathione. We show here that exemestane transcriptionally activates NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), typical chemoprotective gene products, in a wide variety of mouse, rat, and human cells. It protects several cell lines against oxidative toxicity of tert-butyl hydroperoxide and 4-hydroxynonenal, against free radical damage arising from hypoxia–reoxygenation, and against UVA radiation damage. Exemestane also inhibits the inflammatory increases in inducible nitric oxide synthase (iNOS) in mouse macrophages exposed to LPS (lipopolysaccharide), thereby resembling the isothiocyanate sulforaphane derived from broccoli. Remarkably, combinations of exemestane and sulforaphane act highly synergistically, and this property is also displayed by several other phytochemicals. Thus, exemestane has a wide range of previously unrecognized protective activities, probably unrelated to aromatase inhibition. Its potential for reducing the risk, not only of breast cancer, but also of other chronic diseases that arise from inflammation, oxidative stress, and DNA-damaging electrophiles, requires exploration, particularly in view of the synergism with other phytochemicals. PMID:24191056

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention.

PubMed

Liu, Hua; Talalay, Paul

2013-11-19

Exemestane (6-methyleneandrosta-1,4-diene-3,17-dione) is a synthetic steroidal inhibitor of the aromatase reaction that catalyzes the terminal and rate-limiting step of the biosynthesis of estrogens. It is active clinically in preventing, delaying progression of, and treating mammary cancers, many of which are estrogen receptor-positive. A striking feature of the structure of exemestane is an extended system of conjugated Michael reaction functions, which is also characteristic of inducers of a broad network of chemoprotective genes regulated by the Keap1 (Kelch-like ECA-associated protein)/Nrf2 (nuclear factor E2-related factor 2)/ARE (antioxidant response element) signaling system. These genes are largely involved in xenobiotic metabolism and antioxidative and anti-inflammatory protection, as well as the synthesis and reduction of glutathione. We show here that exemestane transcriptionally activates NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), typical chemoprotective gene products, in a wide variety of mouse, rat, and human cells. It protects several cell lines against oxidative toxicity of tert-butyl hydroperoxide and 4-hydroxynonenal, against free radical damage arising from hypoxia-reoxygenation, and against UVA radiation damage. Exemestane also inhibits the inflammatory increases in inducible nitric oxide synthase (iNOS) in mouse macrophages exposed to LPS (lipopolysaccharide), thereby resembling the isothiocyanate sulforaphane derived from broccoli. Remarkably, combinations of exemestane and sulforaphane act highly synergistically, and this property is also displayed by several other phytochemicals. Thus, exemestane has a wide range of previously unrecognized protective activities, probably unrelated to aromatase inhibition. Its potential for reducing the risk, not only of breast cancer, but also of other chronic diseases that arise from inflammation, oxidative stress, and DNA-damaging electrophiles, requires exploration, particularly in view of the synergism with other phytochemicals.

Styrene-spaced copolymers including anthraquinone and β-O-4 lignin model units: synthesis, characterization and reactivity under alkaline pulping conditions.

PubMed

Megiatto, Jackson D; Cazeils, Emmanuel; Ham-Pichavant, Frédérique; Grelier, Stéphane; Gardrat, Christian; Castellan, Alain

2012-05-14

A series of random copoly(styrene)s has been synthesized via radical polymerization of functionalized anthraquinone (AQ) and β-O-4 lignin model monomers. The copolymers were designed to have a different number of styrene spacer groups between the AQ and β-O-4 lignin side chains aiming at investigating the distance effects on AQ/β-O-4 electron transfer mechanisms. A detailed molecular characterization, including techniques such as size exclusion chromatography, MALDI-TOF mass spectrometry, and (1)H, (13)C, (31)P NMR and UV-vis spectroscopies, afforded quantitative information about the composition of the copolymers as well as the average distribution of the AQ and β-O-4 groups in the macromolecular structures. TGA and DSC thermal analysis have indicated that the copolymers were thermally stable under regular pulping conditions, revealing the inertness of the styrene polymer backbone in the investigation of electron transfer mechanisms. Alkaline pulping experiments showed that close contact between the redox active side chains in the copolymers was fundamental for an efficient degradation of the β-O-4 lignin model units, highlighting the importance of electron transfer reactions in the lignin degradation mechanisms catalyzed by AQ. In the absence of glucose, AQ units oxidized phenolic β-O-4 lignin model parts, mainly by electron transfer leading to vanillin as major product. By contrast, in presence of glucose, anthrahydroquinone units (formed by reduction of AQ) reduced the quinone-methide units (issued by dehydration of phenolic β-O-4 lignin model part) mainly by electron transfer leading to guaiacol as major product. Both processes were distance dependent.

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

PubMed

Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

2017-09-26

Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile and bio-energetic homeostasis.

Epigallocatechin gallate incorporation into lignin enhances the alkaline delignification and enzymatic saccharification of cell walls

PubMed Central

2012-01-01

Background Lignin is an integral component of the plant cell wall matrix but impedes the conversion of biomass into biofuels. The plasticity of lignin biosynthesis should permit the inclusion of new compatible phenolic monomers such as flavonoids into cell wall lignins that are consequently less recalcitrant to biomass processing. In the present study, epigallocatechin gallate (EGCG) was evaluated as a potential lignin bioengineering target for rendering biomass more amenable to processing for biofuel production. Results In vitro peroxidase-catalyzed polymerization experiments revealed that both gallate and pyrogallyl (B-ring) moieties in EGCG underwent radical cross-coupling with monolignols mainly by β–O–4-type cross-coupling, producing benzodioxane units following rearomatization reactions. Biomimetic lignification of maize cell walls with a 3:1 molar ratio of monolignols and EGCG permitted extensive alkaline delignification of cell walls (72 to 92%) that far exceeded that for lignified controls (44 to 62%). Alkali-insoluble residues from EGCG-lignified walls yielded up to 34% more glucose and total sugars following enzymatic saccharification than lignified controls. Conclusions It was found that EGCG readily copolymerized with monolignols to become integrally cross-coupled into cell wall lignins, where it greatly enhanced alkaline delignification and subsequent enzymatic saccharification. Improved delignification may be attributed to internal trapping of quinone-methide intermediates to prevent benzyl ether cross-linking of lignin to structural polysaccharides during lignification, and to the cleavage of ester intra-unit linkages within EGCG during pretreatment. Overall, our results suggest that apoplastic deposition of EGCG for incorporation into lignin would be a promising plant genetic engineering target for improving the delignification and saccharification of biomass crops. PMID:22889353

Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase.

PubMed

Yang, Shaojun; Jan, Yi-Hua; Mishin, Vladimir; Richardson, Jason R; Hossain, Muhammad M; Heindel, Ned D; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

2015-03-01

Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both sepiapterin reduction and redox cycling. The most potent inhibitors of sepiapterin reduction (IC50s = 31-180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37-19.4 μM) were required to inhibit redox cycling, presumably because of distinct mechanisms of sepiapterin reduction and redox cycling. In PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibited both BH2/BH4 biosynthesis and redox cycling mediated by SPR. Inhibition of BH2/BH4 resulted in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine. Sulfathiazole (200 μM) markedly suppressed neurotransmitter production, an effect reversed by BH4. These data suggest that SPR and BH4-dependent enzymes, are "off-targets" of sulfa drugs, which may underlie their untoward effects. The ability of the sulfa drugs to inhibit redox cycling may ameliorate ROS-mediated toxicity generated by redox active drugs and chemicals, contributing to their anti-inflammatory activity. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.