Redox Control Research Articles

Unraveling seasonal shifts in microbial and geochemical mediated arsenic mobilization at the estuarine sediment-water interface under redox changes

The mobilization of arsenic (As) at the sediment-water interface (SWI) is crucial for determining the accumulation of dissolved As to potentially toxic levels. However, the specific impacts of redox processes involving iron (Fe) and sulfur (S), as well as microbial activities occurring in sediments, on As mobilization at the marine SWI remain poorly understood. In this study, we investigated As mobilization at the SWI in the Changjiang Estuary during three different seasons with different benthic redox conditions. The preferential reduction of arsenate (As(V)) to arsenite (As(III)) and subsequent re-adsorption onto newly formed crystalline Fe oxides restricted As release in the As(V) reduction layer. Enhanced Fe(III) reduction in the Fe(III) reduction layer contributed to As release, while the presence of low As-high Fe-high SO42− levels resulted in As removal through adsorption onto pyrite in the sulfate reduction layer. Analysis of functional genes indicated that As(V) in sediments was released into porewater through the reductive dissolution of As(V)-bearing Fe(III) oxides by Geobacter species, followed by microbial reduction of the liberated As(V) to As(III) by microbes carrying the arrA gene. The dominant pathway governing As mobilization at the SWI in the Changjiang Estuary shifted from microbial reduction control during the hypoxic summer to Fe redox control during the aerobic autumn and winter. These findings provide valuable insights into the complex mechanisms driving As mobilization and highlight the importance of considering seasonal variations in understanding As dynamics at the marine SWI.

Uranium isotopes in non-euxinic shale and carbonate reveal dynamic Katian marine redox conditions accompanying a decrease in biodiversity prior to the Late Ordovician Mass Extinction

The Late Ordovician mass extinction (LOME) is the first major mass extinction event in the Phanerozoic. However, global biodiversity started to decline during the Katian (prior to the LOME) and coeval global ocean redox conditions are not well understood. The deposition of Katian organic-rich sedimentary rocks, namely the calcareous Collingwood Member and overlying siliciclastic Rouge River Member, was triggered by the concurrent Taconic Orogeny in southern Ontario (Canada) near the interface between the epicratonic Appalachian and Michigan basins. In this study, we used geochemical elemental proxies and uranium isotope compositions (δ238U) to reconstruct local and global ocean redox states during deposition of both units at seven drill core localities throughout southern Ontario. Local redox conditions are revealed by several proxies (redox sensitive trace metals, Fe speciation, and Corg:P ratios). Collectively, these proxies suggest spatiotemporal redox variations for the Collingwood Member: O2-deficient conditions (non-euxinic) for the deep waters of the Appalachian and Michigan basins and mostly oxic-suboxic conditions for the shallow waters. In contrast, predominantly oxic-suboxic conditions are suggested for the Rouge River Member.Global ocean redox conditions are inferred from the δ238U of both units. The coeval seawater δ238U value during Collingwood Member deposition is estimated to be from ∼−0.87‰ to ∼−0.64‰, based on both carbonate δ238U (samples leached with 1 N HCl) and δ238Ubulk-non-detrital data (corrected from the bulk δ238U). Particularly, the δ238Ubulk-non-detrital data of the Collingwood Member from multiple cores (both shallow and deep waters) are positively correlated with elemental redox proxies, suggesting a local redox control on δ238U offsets between sediments and water columns. In contrast, the δ238Ubulk-non-detrital of the suboxic Rouge River Member (average = −0.32 ± 0.12‰) from several cores do not correlate with local redox proxies. The coeval seawater δ238U during Rouge River Member deposition is estimated between −0.62 ± 0.12‰ and −0.42 ± 0.12‰ assuming a δ238U offset of 0.1–0.3‰ as observed between modern suboxic sediments and seawater. For this range of seawater δ238U, a three-sink U isotope mass balance model suggests a contraction of global euxinic seafloor area from deposition of the Collingwood Member (0.5–31.6%; median = 1.0–14.2%) to the Rouge River Member (0.2–2.0%; median = 0.3–1.0%), which could have been associated with the concurrent Taconic Orogeny. Collectively, global marine redox proxy data (i.e., δ98Mo, δ238U) from this and previous studies imply dynamic Katian ocean redox conditions during the decrease of metazoan biodiversity prior to the LOME. As a similar extent of global ocean euxinia during the LOME2 also occurred episodically during the Katian but did not result in LOME2-like mass extinctions, it is suggested that other factors (e.g., climate), besides expanded ocean euxinia, could have contributed to the second phase of the LOME.

Redox control of System XC- by glutaredoxin via deglutathionylation of ovarian tumor deubiquitinase 1

Redox control of System XC- by glutaredoxin via deglutathionylation of ovarian tumor deubiquitinase 1

A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions.

ConspectusTransition-metal catalyzed cross-coupling reactions are fundamental reactions in organic chemistry, facilitating strategic bond formations for accessing natural products, organic materials, agrochemicals, and pharmaceuticals. Redox chemistry enables access to elusive cross-coupling mechanisms through single-electron processes as an alternative to classical two-electron strategies predominated by palladium catalysis. The seminal reports of Baran, MacMillan, Doyle, Molander, Weix, Lin, Fu, Reisman, and others in merging redox perturbation (photochemical, electrochemical, and purely chemical) with catalysis are pivotal to the current resurgence and mechanistic understanding of first-row transition metal-based catalysis. The hallmark of this redox platform is the systematic modulation of transition-metal oxidation states by a photoredox catalyst or at a heterogeneous electrode surface. Electrocatalysis and photocatalysis enhance transition metal catalysis' capacity for bond formation through electron- or energy-transfer processes that promote otherwise challenging elementary steps or elusive mechanisms. Cross-coupling conditions promoted by electrocatalysis and photocatalysis are mild, and bond formation proceeds with exceptionally high chemoselectivity and wide functional group tolerance. The interfacing of abundant first-row transition-metal catalysis with electrocatalysis and photocatalysis has brought about a paradigm shift in cross-coupling technology as practitioners are quickly applying these tools in synthesizing fine chemicals and pharmaceutically relevant motifs. In particular, the merger of Ni catalysis with electro- and photochemistry ushered in a new era for carbon-carbon and carbon-heteroatom cross-couplings with expanded generality compared to their thermally driven counterparts. Over the past decade, we have developed enabling photo- and electrochemical methods throughout our combined research experience in industry (BMS, AstraZeneca) and academia (Professor Baran, Scripps Research) in cross-disciplinary collaborative environments. In this Account, we will outline recent progress from our past and present laboratories in photo- and electrochemically mediated Ni-catalyzed cross-couplings. By highlighting these cross-coupling methodologies, we will also compare mechanistic features of both electro- and photochemical strategies for forging C(sp2)-C(sp3), C(sp3)-C(sp3), C-O, C-N, and C-S bonds. Through these side-by-side comparisons, we hope to demystify the subtle differences between the two complementary tools to enact redox control over transition metal catalysis. Finally, building off the collective experience of ourselves and the rest of the community, we propose a tactical user guide to photo- and electrochemically driven cross-coupling reactions to aid the practitioner in rapidly applying such tools in their synthetic designs.

Redox control of signalling responses to contractile activity and aging in skeletal muscle

During aging loss of skeletal muscle mass and function has a significant effect of an individual’s quality of life and ability to maintain independence. Both loss of muscle fibres and atrophy of the remaining fibres play a role in the muscle decline and this is associated with loss of motor units and a reduction in the number of motor neurons. Increased oxidative damage has long been claimed to be associated with aging and many studies have reported increased amounts of oxidative damage markers are found in tissues from old organisms. Reactive oxygen species (ROS) are recognised to play a major role in cell signalling and in muscle ROS generated during contractile play an important role in signalling adaptations to contractile activity. These ’redox-regulated’ pathways are beneficial adaptations which are attenuated during aging. This review will briefly cover what is currently known about the mechanisms underlying these muscle adaptations to exercise, how they are affected by aging and assess the importance of these pathways in age-related loss of skeletal muscle mass and function.

SUMOylation of the ubiquitin ligase component KEAP1 at K39 upregulates NRF2 and its target function in lung cancer cell proliferation

Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is important for the expression of genes associated with oxidative stress. The levels of NRF2 are controlled by Kelch-like ECH-associated protein 1 (KEAP1)-dependent degradation. Although oxidative stress is known to suppress KEAP1 activity to stabilize the levels of NRF2, the mechanism for this control is unclear. Here, we identify that KEAP1 is modified by SUMO1 at the lysine residue position 39 (K39). Arginine replacement of this lysine (K39R) in KEAP1 did not affect its stability, subcellular localization, or dimerization but promoted the formation of the Cullin 3 ubiquitin ligase and increased NRF2 ubiquitination. This was accompanied by decreased NRF2 expression. Gene reporter assays showed that the transcription of antioxidant response elements was heightened in KEAP1-WT cells compared to cells expressing the KEAP1-K39R SUMO1 substrate mutant. Consistent with this, chromatin immunoprecipitation assays revealed higher NRF2 binding to the promoter regions of antioxidant genes in cells expressing the KEAP1-WT compared to the KEAP1-K39R mutant protein in H1299 lung cancer cell. The significance of this suppression of KEAP1 activity by its SUMOylation was tested in a subcutaneous tumor model of H1299 lung cancer cell lines that differentially expressed the WT and K39R KEAP1 constructs. This model showed that mutating the SUMOylation site on KEAP1 altered the production of reactive oxygen species and suppressed tumor growth. Taken together, our study recognizes that NRF2-dependent redox control is regulated by the SUMOylation of KEAP1. These findings identify a potential new therapeutic option to counteract oxidative stress.

Therapeutic Targeting of Mitochondrial Plasticity and Redox Control to Overcome Cancer Chemoresistance.

Mitochondria are subcellular organelles performing essential metabolic functions contributing to cellular bioenergetics and regulation of cell growth or death. The basic mitochondrial function in fulfilling the need for cell growth and vitality is evidenced by the conditional state whereby cancer cells with depleted mitochondrial DNA (rho zero cells) are no longer capable of forming tumors until newly recruited mitochondria are internalized into the rho zero cells. Herein lies the absolute dependency on mitochondria for tumor growth. In addition, mitochondria are key regulators of cell death (by apoptosis, necroptosis, or other forms of cell death) and are therefore important targets for anticancer therapy. Mitochondrial plasticity regulating their state of fusion or fission is also key to the chemoresistance properties of cancer cells by promoting pro-survival pathways enabling the mitochondria to mitigate against the cellular stresses and extreme conditions within the tumor microenvironment caused by chemotherapy, hypoxia, or oxidative stress. This review discusses many characteristics of mitochondria, the processes and pathways controlling the dynamic changes occurring in the morphology of mitochondria, the roles of reactive oxygen species, and their relationship with mitochondrial fission or fusion. It also examines the relationship of redox to mitophagy when mitochondria become compromised and its effect on cancer cell survival, stemness and the changes accompanying malignant progression from primary tumors to metastatic disease. A challenging question that arises is whether the changes in mitochondrial dynamics and their regulation can provide opportunities for improving drug targeting during cancer treatment and enhancing survival outcomes.

Solid-State Electrochemistry on Supramolecular Assemblies with Strong Isotropic Property

It has been mathematically proven that only honeycomb, diamond, and K4 lattices have a special symmetry called "strong isotropy". Note that crystallographic symmetry is determined only by the position of atoms, while strong isotropy is governed by both the position of atoms and bonds. The K4 lattice, called by various names such as gyroid lattice and srs network, is characterized by the fact that it exhibits chirality. It is recognized that their mathematically-defined “line graphs” correspond to kagome, hyper-kagome, and pyrochlore lattices, respectively, which are well known as spin frustration lattices. This relation suggests that the materials with the strong isotropic lattices possess “hidden” frustration. It is also noteworthy that the band structure of the three lattices contains exotic band dispersions such as Dirac cones due to their lattice symmetry, and that they possess porous structures. From this perspective, we proposed to form the supramolecular assemblies with the with strong isotropic property, and to carry out electrochemical valence control for realizing exotic physical properties such as Dirac electron, spin frustration, etc.In this presentation, we will explain our previous works on the solid-state electrochemistry of LiPc as an introduction. Then, we will report the rational synthesis of the molecule-based honeycomb and K4 structures, using MOF/COF- and supramolecular-chemistry, the nanohybridization using their porous structures, the physical properties such as spin frustration and circularly polarized luminescence, and the solid-state electrochemical redox control on them without destroying the original frameworks.

Towards a structural investigation of MamP, a key player in redox control during magnetosome maturation

Towards a structural investigation of MamP, a key player in redox control during magnetosome maturation

Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

To evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ Tcells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD+ boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4+ Tcell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD+ boosting in CD4+ Tcell-linked inflammation.

Redox controls on anaerobic ammonium oxidation coupled to reduction of natural organic matter in paddy ecosystems

Redox controls on anaerobic ammonium oxidation coupled to reduction of natural organic matter in paddy ecosystems

In Situ Construction of Ferrocene-Containing Membrane-Bound Nanofibers for the Redox Control of Cancer Cell Death and Cancer Therapy.

Precise manipulation of cancer cell death by harnessing reactive oxygen species (ROS) is a promising strategy to defeat malignant tumors. However, it is quite difficult to produce active ROS with spatial precision and regulate their biological outcomes. We succeed here in selectively generating short-lived and lipid-reactive hydroxyl radicals (•OH) adjacent to cancer cell membranes, successively eliciting lipid peroxidation and ferroptosis. DiFc-K-pY, a phosphorylated self-assembling precursor that consists of two branched Fc moieties and interacts specifically with epidermal growth factor receptor, can in situ produce membrane-bound nanofibers and enrich ferrocene moieties on cancer cell membranes in response to alkaline phosphatase. Within the acidic tumor microenvironment, DiFc-K-pY nanofibers efficiently convert tumoral H2O2 to active •OH around the target cell membranes via Fenton-like reactions, leading to lipid peroxidation and ferroptosis with good cellular selectivity. Our strategy successfully prevents tumor progression with acceptable biocompatibility through intratumoral administration.

In-situ redox conditions in hydrothermal diamond-anvil cell experiments using various metal gaskets

Hydrothermal diamond-anvil cells (HDACs) have been widely used in various research fields since they were introduced in 1993. Unlike temperature (T) and pressure (P), the redox states of the samples in HDAC experiments were poorly controlled or measured; they were usually estimated by observing the reduction/disappearance of redox-sensitive mineral(s) (e.g., Mo metal) and corresponding formation and growth of such mineral(s) (e.g., MoO2) without in-situ redox measurement. In this study, we demonstrated the generation of H2 during experiments using various metal gaskets, including inert (Re) and chemically more reactive metals (Ni, Co, Mo, and W), in the pure H2O system under various P-T conditions. A technique for quantitative Raman spectroscopic analysis of H2 in HDAC is designed. Based on this technique, the oxygen fugacity (fO2) values of Mo-MoO2 buffer at the experimental P-T conditions were then calculated from these measured H2 pressures. We demonstrated that steady-state redox control can be maintained at a fixed T between 400 and 500 °C in HDAC experiments using a Mo gasket for durations of up to two hours and for those using a Re gasket with an additional Mo rod in the sample between 400 and 800 °C for durations of up to 90 min, regardless of the considerable changes in sample pressure. This demonstration was established by the balance between the rates of H2 generation and H2 loss from the sample chamber. The loss of H2 enhanced the consumption of H2O and therefore reduced the sample pressures during the experiments.We believe that hydrogen contents in every HDAC experiment, which attempt to control the redox state, need in situ measurement, then estimate the real redox state and compare it to thermodynamic equilibrium prediction. To enhance in situ redox control and measurements, modifications of HDAC are required for improving the quantitative Raman spectroscopic analysis technique in both sensitivity and accuracy.

Effect of Ti‐metal addition on hot‐isostatically pressed (HIPed) Synroc‐C

AbstractSynroc, a candidate nuclear wasteform and Synroc technology, a waste treatment solution utilizing hot‐isostatic pressing (HIPing) have significant potential for the immobilisation of challenging nuclear wastes from both current and innovative reactors and fuel cycles. Hot isostatic press (HIP) consolidation is undertaken within sealed metal HIP canisters, where metal buffers (e.g., Ti, Fe and Ni) can be incorporated to control the redox environment within the canister. This study, for the first time, reports the effect of varying Ti‐metal addition (0, 2, 4, and 8 wt.%) on phase formation, microstructural characteristics, and wasteform performance for HIP consolidated Synroc‐C containing 20 wt.% simulated PUREX type (PW‐4b) high level waste. Quantitative X‐ray diffraction analysis, scanning electron microscopy‐energy dispersive X‐ray spectroscopy (EDS) and transmission electron microscopy‐EDS analyses were undertaken for analytical investigations. The chemical durability of the samples was assessed using ASTM C1220‐21 standard test. Hot‐isostatically pressed (HIPed) samples with 0 and 8 wt.% Ti added for redox control produced unfavourable phase formation. However, the HIPed samples with Ti additions of 2 and 4 wt.% as a redox buffer showed the desired phase formation of Synroc‐C without any significant change to the partitioning of waste elements among the phases along with compatible durability results, when compared to previous literature for hot uniaxial pressing (HUPed) or sintered materials.

Calredoxin regulates the chloroplast NADPH-dependent thioredoxin reductase in Chlamydomonas reinhardtii.

Calredoxin (CRX) is a calcium (Ca2+)-dependent thioredoxin (TRX) in the chloroplast of Chlamydomonas (Chlamydomonas reinhardtii) with a largely unclear physiological role. We elucidated the CRX functionality by performing in-depth quantitative proteomics of wild-type cells compared with a crx insertional mutant (IMcrx), two CRISPR/Cas9 KO mutants, and CRX rescues. These analyses revealed that the chloroplast NADPH-dependent TRX reductase (NTRC) is co-regulated with CRX. Electron transfer measurements revealed that CRX inhibits NADPH-dependent reduction of oxidized chloroplast 2-Cys peroxiredoxin (PRX1) via NTRC and that the function of the NADPH-NTRC complex is under strict control of CRX. Via non-reducing SDS-PAGE assays and mass spectrometry, our data also demonstrated that PRX1 is more oxidized under high light (HL) conditions in the absence of CRX. The redox tuning of PRX1 and control of the NADPH-NTRC complex via CRX interconnect redox control with active photosynthetic electron transport and metabolism, as well as Ca2+ signaling. In this way, an economic use of NADPH for PRX1 reduction is ensured. The finding that the absence of CRX under HL conditions severely inhibited light-driven CO2 fixation underpins the importance of CRX for redox tuning, as well as for efficient photosynthesis.

TP53/p53 Facilitates Stress-Induced Exosome and Protein Secretion by Adipocytes.

Besides the secretion of fatty acids, lipolytic stimulation of adipocytes results in the secretion of triglyceride-rich extracellular vesicle (AdEVs) and some free proteins (e.g., Fatty Acid Binding Protein 4) that in sum affect adipose homeostasis as well as the development of metabolic disease. At the mechanistic level, lipolytic signals activate p53 in an ATGL-dependent manner and pharmacologic inhibition of p53 attenuates AdEV protein and FABP4 secretion. Mass spectrometry analyses of the lipolytic secretome identified proteins involved in glucose and fatty acid metabolism, translation, chaperone activities as well as redox control. Consistent with a role for p53 in adipocyte protein secretion, activation of p53 by the MDM2 antagonist nutlin potentiated AdEV particles and non-AdEV protein secretion from cultured 3T3-L1 or OP9 adipocytes while the levels of FABP4 and AdEV proteins were significantly reduced in serum from p53-/- mice compared to wild-type controls. The genotoxin doxorubicin increased AdEV protein and FABP4 secretion in a p53-dependent manner and DNA repair-depleted ERCC1-/Δ haploinsufficient mice expressed elevated p53 in adipose depots, along with significantly increased serum FABP4. In sum, these data suggest that lipolytic signals, and cellular stressors such as DNA damage, facilitate AdEV protein and FABP4 secretion by adipocytes in a p53-dependent manner.

Redox and mineral controls on Fe and Ti isotopic fractionations during calc-alkaline magmatic differentiation

Titanium and Fe isotopic compositions of lavas from a calc-alkaline differentiation suite and corresponding mineral separates from the Rindjani Volcano, Indonesia show that Fe and Ti isotopic fractionations between minerals and melts are lower than those recorded in other suites at all stages of differentiation. The limited isotopic fractionation for Ti is likely due to low-Ti magnetite and clinopyroxene being the dominant carriers of Ti in Rindjani lavas, as these minerals are thought to have limited equilibrium Ti isotopic fractionation relative to silicate magmas. Other magmatic differentiation suites controlled by removal of Ti-rich magnetite and characterized by a lesser role of clinopyroxene have larger Ti isotopic fractionations. This effect is an indirect consequence of the elevated Fe3+/Fe2+ ratio of calc-alkaline magmas such as Rindjani, which promotes Fe3+ incorporation into magnetite at the expense of Fe2+-Ti4+ pairs, such that increased oxygen fugacity will subdue Ti isotopic fractionation in global magmatic series. Similarly, we find negligible Fe isotopic fractionation in Rindjani bulk rocks and mineral separates, unlike previous studies. This is also likely due to the oxidized nature of the Rindjani differentiation suite, which leads to similar Fe3+/Fe2+ ratios in melt and minerals and decreases overall mineral-melt Fe fractionation factors. Paired Ti and Fe isotopic analyses may therefore represent a powerful tool to assess oxygen fugacity during differentiation, independent from Fe 3+ determinations of erupted samples.

Click chemistry-based thiol redox proteomics reveals significant cysteine reduction induced by chronic ethanol consumption

In the U.S., alcohol-associated liver disease (ALD) impacts millions of people and is a major healthcare burden. While the pathology of ALD is unmistakable, the molecular mechanisms underlying ethanol hepatotoxicity are not fully understood. Hepatic ethanol metabolism is intimately linked with alterations in extracellular and intracellular metabolic processes, specifically oxidation/reduction reactions. The xenobiotic detoxification of ethanol leads to significant disruptions in glycolysis, β-oxidation, and the TCA cycle, as well as oxidative stress. Perturbation of these regulatory networks impacts the redox status of critical regulatory protein thiols throughout the cell. Integrating these key concepts, our goal was to apply a cutting-edge approach toward understanding mechanisms of ethanol metabolism in disrupting hepatic thiol redox signaling. Utilizing a chronic murine model of ALD, we applied a cysteine targeted click chemistry enrichment coupled with quantitative nano HPLC-MS/MS to assess the thiol redox proteome. Our strategy reveals that ethanol metabolism largely reduces the cysteine proteome, with 593 cysteine residues significantly reduced and 8 significantly oxidized cysteines. Ingenuity Pathway Analysis demonstrates that ethanol metabolism reduces specific cysteines throughout ethanol metabolism (Adh1, Cat, Aldh2), antioxidant pathways (Prx1, Mgst1, Gsr), as well as many other biochemical pathways. Interestingly, a sequence motif analysis of reduced cysteines showed a correlation for hydrophilic, charged amino acids lysine or glutamic acid nearby. Further research is needed to determine how a reduced cysteine proteome impacts individual protein activity across these protein targets and pathways. Additionally, understanding how a complex array of cysteine-targeted post-translational modifications (e.g., S–NO, S-GSH, S–OH) are integrated to regulate redox signaling and control throughout the cell is key to the development of redox-centric therapeutic agents targeted to ameliorate the progression of ALD.

Voltage-driven control of single-molecule keto-enol equilibrium in a two-terminal junction system

Keto-enol tautomerism, describing an equilibrium involving two tautomers with distinctive structures, provides a promising platform for modulating nanoscale charge transport. However, such equilibria are generally dominated by the keto form, while a high isomerization barrier limits the transformation to the enol form, suggesting a considerable challenge to control the tautomerism. Here, we achieve single-molecule control of a keto-enol equilibrium at room temperature by using a strategy that combines redox control and electric field modulation. Based on the control of charge injection in the single-molecule junction, we could access charged potential energy surfaces with opposite thermodynamic driving forces, i.e., exhibiting a preference for the conducting enol form, while the isomerization barrier is also significantly reduced. Thus, we could selectively obtain desired and stable tautomers, which leads to significant modulation of the single-molecule conductance. This work highlights the concept of single-molecule control of chemical reactions on more than one potential energy surface.

Subacute exposure to Roundup® changes steroidogenesis and gene expression of the glutathione-glutaredoxin system in rat ovaries: Implications for ovarian toxicity of this glyphosate-based herbicide

Studies have indicated that glyphosate induces endocrine disruption and may adversely affect the male reproductive system. However, evidence of its effects on ovarian function is poorly understood so far, making further studies necessary on the mechanisms of the glyphosate toxicity in the female reproductive system. The aim of this work was to evaluate the effect of a subacute exposure (28 days) to the glyphosate-based formulation Roundup® (1.05, 10.5 and 105 μg/kg b.w. of glyphosate) on steroidogenesis, oxidative stress, systems involved in cell redox control and histopathological parameters in rat ovaries. Hence we quantify plasma estradiol and progesterone by chemiluminescence; non-protein thiol levels, TBARS, superoxide dismutase and catalase activity by spectrophotometry; gene expression of steroidogenic enzymes and redox systems by real-time PCR; and ovarian follicles by optical microscopy. Our results demonstrated that oral exposure increased progesterone levels and the mRNA expression of 3β-hydroxysteroid dehydrogenase. Histopathological analysis revealed a decrease in the number of primary follicles and an increase in the number of corpus luteum in rats exposed to Roundup®. An imbalance of the oxidative status was also evidenced by decreasing the catalase activity at all groups exposed to the herbicide. Increased lipid peroxidation and gene expression of glutarredoxin and decreased of glutathione reductase were also observed. Our results indicate that Roundup® causes endocrine disruption of hormones related to female fertility and reproduction and changes the oxidative status by altering antioxidant activity, inducing lipid peroxidation, as well as changing the gene expression of the glutathione-glutarredoxin system in rat ovaries.