Why 1,2‑quinone derivatives are more stable than their 2,3‑analogues?

In this work, we have studied the relative stability of 1,2- and 2,3-quinones. While 1,2-quinones have a closed-shell singlet ground state, the ground state for the studied 2,3-isomers is open-shell singlet, except for 2,3-naphthaquinone that has a closed-shell singlet ground state. In all cases, 1,2-quinones are more stable than their 2,3-counterparts. We analyzed the reasons for the higher stability of the 1,2-isomers through energy decomposition analysis in the framework of Kohn–Sham molecular orbital theory. The results showed that we have to trace the origin of 1,2-quinones’ enhanced stability to the more efficient bonding in the π-electron system due to more favorable overlap between the SOMOπ of the ·C4n−2H2n–CH·· and ··CH–CO–CO· fragments in the 1,2-arrangement. Furthermore, whereas 1,2-quinones present a constant trend with their elongation for all analyzed properties (geometric, energetic, and electronic), 2,3-quinone derivatives present a substantial breaking in monotonicity.European Union in the framework of European Social Fund through the Warsaw University of Technology Development Programme. O.A. S., H. S. and T.M. K

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

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

Beyond Intent: Technology Adoption and Appropriation by University Staff

In this paper, we propose a model for understanding adoption and appropriation of technology. We describe a university-wide system that is designed for faculty and students, but which has been adopted by staff, followed by a survey study and some preliminary results

How do we Bridge the Gap between the Five Generations in the Workforce and Reduce Biases around Age?

In today’s organizations, as many as four to five generations work together. The multigenerational workplace is vulnerable to age biases that can lead to lower job and organizational satisfaction. These biases are of particular harm to older employees, whose performance suffers the most under biased managers. However, gaps between generations may be smaller than perceived, with many generations sharing similarities in values and organizational commitment. Even if the “generation gap” is small, eliminating bias and creating a diverse work environment is important for organizational success

Efficient photochemical activity and strong dichroism of single crystals of reaction centers from Rhodopseudomonas viridis

Crystallized reaction centers from Rhodopseudomonas viridis (i) are photochemically active with electron transfer from the special pair to the quinones, (ii) show dichroism giving valuable information on the orientation of the different chromophores and (iii) allow chemical treatment in the crystalline phase

Glutathione (GSH) conjugates with dopamine (DA)-derived quinones to form reactive or non-reactive GSH-conjugates

In this study we demonstrate for the first time that GSH could rapidly conjugate with dopamine (DA)-derived DA-o-quinones without enzymatic catalysis to form short-lived intermediate GSH-conjugates (2-S-GSH-DA-o-quinone and 5-S-GSH-DA-o-quinone). These intermediate GSH-conjugates are unstable and would finally form reactive or non-reactive GSH-conjugates dependent on ambient reductive forces. Under insufficient reductive forces, the intermediate GSH-conjugates could cyclize spontaneously to form reactive 7-S-GSH-aminochrome (7-S-GSH-AM). The 7-S-GSH-AM is so reactive that it could further react with another GSH to form 4,7-bi-GSH-5,6-dihydroindole. Its reactivity could also abrogate tyrosinase activity in solutions. In addition, the 7-S-GSH-AM could further undergo internal rearrangement to form non-reactive 7-S-GSH-5,6-dihydroindole. From these novel findings, we propose two detrimental positive feedback loops involving accelerated DA oxidation, increased GSH consumption and impaired GSH detoxification efficiency, as the underlying chemical explanation for dopaminergic neuron degeneration in Parkinson's disease

Synthetic Strategies to Terpene Quinones/Hydroquinones

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

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus

Aims: Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen Staphylococcus aureus. Results: Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the S. aureus transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The SACOL2531-29 operon was most strongly upregulated by MHQ and was renamed as mhqRED operon based on its homology to the Bacillus subtilis locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the mhqRED operon, which confers quinone and antimicrobial resistance in S. aureus. The mhqRED operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9–9 bp inverted repeat (MhqR operator) upstream of the mhqRED operon and is inactivated by MHQ in vitro, which does not involve a thiol-based mechanism. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the mhqR mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections. Innovation: Our results provide a link between quinone and antimicrobial resistance via the MhqR regulon of S. aureus. Conclusion: The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of S. aureus under long-term infections

The New Opiate Epidemic

On the subject of narcotics, American public discourse is prone to alarmism, but it is not an exaggeration to say that the United States is currently experiencing an epidemic of opiate addiction. To be exact, we are in the grip of two related epidemics: one involving legal, regulated prescription painkillers, and the other involving black market heroin. Chemically, these two types of drugs have a great deal in common, and both are devastatingly addictive. But the rise in pill addiction and the rise in heroin addiction are linked on a deeper causal level, as well.Drug overdoses now kill more Americans than car accidents, and most of those overdoses are from opiates. Heroin-related deaths have quadrupled since 2000, leading to what the New York Times has suggested may be "the worst drug overdose epidemic in United States history." Former attorney general Eric Holder described the rise in heroin addiction as a "public health crisis," with heroin overdoses leading to 10,574 deaths in 2014.But in fact, the spike in heroin abuse is an outgrowth of a much broader and in some ways more pernicious problem -- the widespread addiction to prescription painkillers. Pharmaceutical opioid overdoses have also quadrupled since 2000, leading to 18,893 deaths in 2014 -- almost double the number of heroin overdoses for the same year. The suppliers of these drugs are not street-corner dealers, but ostensibly respectable physicians, and behind them, multibillion-dollar pharmaceutical companies, with squadrons of lawyers and lobbyists