Quinone Oxidation Research Articles

Tunneling Mechanisms of Quinones in Photosynthetic Reaction Center–Light Harvesting 1 Supercomplexes

In photosynthesis, light energy is absorbed and transferred to the reaction center, ultimately leading to the reduction of quinone molecules through the electron transfer chain. The oxidation and reduction of quinones generate an electrochemical potential difference used for adenosine triphosphate synthesis. The trafficking of quinone/quinol molecules between electron transport components has been a long‐standing question. Here, an atomic‐level investigation into the molecular mechanism of quinol dissociation in the photosynthetic reaction center–light‐harvesting complex 1 (RC–LH1) supercomplexes from Rhodopseudomonas palustris, using classical molecular dynamics (MD) simulations combined with self‐random acceleration MD‐MD simulations and umbrella sampling methods, is conducted. Results reveal a significant increase in the mobility of quinone molecules upon reduction within RC–LH1, which is accompanied by conformational modifications in the local protein environment. Quinol molecules have a tendency to escape from RC–LH1 in a tail‐first mode, exhibiting channel selectivity, with distinct preferred dissociation pathways in the closed and open LH1 rings. Furthermore, comparative analysis of free energy profiles indicates that alternations in the protein environment accelerate the dissociation of quinol molecules through the open LH1 ring. In particular, aromatic amino acids form π‐stacking interactions with the quinol headgroup, resembling the key components in a conveyor belt system. This study provides insights into the molecular mechanisms that govern quinone/quinol exchange in bacterial photosynthesis and lays the framework for tuning electron flow and energy conversion to improve metabolic performance.

Heavily Doped Carbon Nitride Nanocrystal Promotes Visible-Near-Infrared Photosynthesis of Hydrogen Peroxide with Near-Unit Photon Utilization.

Direct photosynthesis of hydrogen peroxide (H2O2) from water and oxygen represents an intriguing alternative to the current indirect process involving the reduction and oxidation of quinones. However, limited light utilization and sluggish charge transfer largely impede overall photocatalytic efficiency. Herein, we present a heavily doped carbon nitride (CNKLi) nanocrystal for efficient and selective photoproduction of H2O2 via a two-electron oxygen reduction reaction (ORR) pathway. CNKLi induces metal-to-ligand charge transfer (MLCT) and electron trapping, which broadens the light absorption to the visible-near-infrared (vis-NIR) spectrum and prolongs the photoelectron lifetime to the microsecond time scale with an exceptional charge diffusion length of ∼1200 nm. Near-unit photoutilization with an apparent quantum yield (AQY) of 100% for H2O2 generation is achieved below 420 nm. Impressively, CNKLi exhibits an appreciable AQY of 16% at 700 nm, which reaches the absorption capacity (∼16%), thus suggesting a near-unit photon utilization <700 nm. In situ characterization and theoretical calculations reveal the facilitated charge transfer from K+ to the heptazine ring skeleton. These findings provide an approach to improve the photosynthetic efficiency of direct H2O2 preparation in the vis-NIR region and expand applications for driving kinetically slow and technologically desirable oxidations or high-value chemical generation.

Construction of core–shell structured CrOx/NiCoxO4 catalyst for low temperature catalytic oxidation of toluene: Understanding the reactivity promotion mechanism of the core–shell interactions

Bimetallic-based spinels are potential materials for toluene oxidation ascribing to their remarkable stability and oxidation activity. However, the insufficient toluene adsorption capacity and limited reactive oxygen species severely restrict their low-temperature catalytic reactivity. This study reports a facile two-step solvothermal strategy for the synthesis of core–shell structured CrOx/NiCoxO4 catalyst, which exhibits excellent toluene oxidation performance with T50 and T90 values of 187 and 218 °C, respectively, and the toluene conversion remains above 90 % at 218 °C for 20 h. The in-situ DRIFTs indicate that the oxidation of toluene to CO2 and H2O follows Mars-van Krevelen (MvK) mechanism, and the rate limiting step is the oxidation of maleic anhydride. The strong interaction between core NiCo2O4 and shell Cr2O3 regulates the morphology of Cr2O3 from particles to porous flocculent structure, which increases the porosity of catalyst and promotes the adsorption of toluene for further oxidation. Moreover, the interaction promotes the charge transfer from NiCo2O4 to Cr2O3, which increases the adsorbed oxygen species contents and the redox capability of the catalyst. A further density functional theory (DFT) calculation confirms that the core NiCo2O4 is the main active component, where the oxygen vacancy formation energy of NiCo2O4 and Cr2O3 decrease from 2.43 and 3.85 eV to 0.31 and 1.52 eV, while the toluene adsorption energy decrease from −0.04 and −0.94 eV to −5.29, and −4.48 eV, respectively, which evidently demonstrates that the formation of core–shell structured CrOx/NiCoxO4 would significantly promote the adsorption and oxidation of toluene, thereby exhibiting excellent low temperature toluene oxidation reactivity.

Migration-mitigated crossover of organic redox anions across a proton-exchange membrane

We introduce a membrane electrolyzer for the generation of hydrogen peroxide via oxygen reduction and catalyst-free oxidation of quinones. The study reports the effect of the applied coulombic forces on ions, which is the origin of crossover.

Oxidative NHC Catalysis: An Unconventional Tool for Macrocyclic Oligoesters Synthesis.

The application of N-heterocyclic carbene (NHC) catalysis under highly diluted oxidative condition to the polycondensation of dialdehydes and diols is herein presented as an alternative, atomeconomical synthetic route to macrocyclic oligoesters (MCOs). The disclosed protocol paves the way to the straightforward access to MCOs, starting from commercial dialdehydes, avoiding the use of toxic diacyl chlorides, commonly employed in traditional MCOs synthetic processes. The method is totally metal-free, takes place in the green Me-THF solvent and requires the use of a fully recyclable quinone oxidant. The protocol versatility is confirmed by the employment of fossil-based and bio-based monomers such as 2,5diformylfuran (DFF), 2,5-bis(hydroxymethyl)furan (BHMF), and isomannide, synthesizing a series of novel and known synthetically relevant macrocyclic oligoesters, fully characterized by NMR and MALDI-TOF MS analysis, with product yields (51-86%) comparable to those obtained by traditional synthetic routes. Finally, to emphasize the synthetic relevance of the target macrocycles, an entropicallydriven ring opening polymerization (ED-ROP) key study has been performed, optimizing the organocatalyzed synthesis of poly(2,5furan-dimethylene 2,5 furandicarboxylate) (PBHMF) with numberaverage molecular weight up to 8200 g mol-1 and 66% isolated yield.

Response of plant defense enzymes against tomato early blight disease

An experiment was conducted to identify the biochemical defense enzymes, viz. catalase (CAT), peroxidase (POX), phenylalanine ammonia lyase (PAL) and total phenol responsible for resistance against A. solani in resistant (cv. H-88-78-1) and susceptible (Punjab Chhuhara) cultivars of tomato after the application of Amistar 25 SC (azoxystrobin 0.1%) during 2015 crop season. Azoxystrobin was applied for their efficacy in inducing defense enzymes in tomato against A. solani. Defense-related enzymes were increased in azoxystrobin pre-treated tomato plants. Early blight resistant tomato plants (cv. H-88-78-1) treated with novel QoI (Quinone oxidation inhibitor) fungicideazxoystrobin inoculated with A. solani under glasshouse conditions showed increased accumulation of defense enzymes, viz. CAT, POX, PAL and total phenol thancontrol plants.

How an assembly factor enhances covalent FAD attachment to the flavoprotein subunit of complex II

The membrane-bound complex II family of proteins is composed of enzymes that catalyze succinate and fumarate interconversion coupled with reduction or oxidation of quinones within the membrane domain. The majority of complex II enzymes are protein heterotetramers with the different subunits harboring a variety of redox centers. These redox centers are used to transfer electrons between the site of succinate–fumarate oxidation/reduction and the membrane domain harboring the quinone. A covalently bound FAD cofactor is present in the flavoprotein subunit, and the covalent flavin linkage is absolutely required to enable the enzyme to oxidize succinate. Assembly of the covalent flavin linkage in eukaryotic cells and many bacteria requires additional protein assembly factors. Here, we provide mechanistic details for how the assembly factors work to enhance covalent flavinylation. Both prokaryotic SdhE and mammalian SDHAF2 enhance FAD binding to their respective apoprotein of complex II. These assembly factors also increase the affinity for dicarboxylates to the apoprotein–noncovalent FAD complex and stabilize the preassembly complex. These findings are corroborated by previous investigations of the roles of SdhE in enhancing covalent flavinylation in both bacterial succinate dehydrogenase and fumarate reductase flavoprotein subunits and of SDHAF2 in performing the same function for the human mitochondrial succinate dehydrogenase flavoprotein. In conclusion, we provide further insight into assembly factor involvement in building complex II flavoprotein subunit active site required for succinate oxidation.

Structural Insight into Evolution of the Quinone Binding Site in Complex II.

The Complex II family encompasses membrane bound succinate:quinones reductases and quinol:fumarate reductases that catalyze interconversion of succinate and fumarate coupled with reduction and oxidation of quinone. These enzymes are found in all biological genres and share a modular structure where a highly conserved soluble domain is bound to a membrane-spanning domain that is represented by distinct variations. The current classification of the complex II family members is based on the number of subunits and co-factors in the membrane anchor (types A-F). This classification also provides insights into possible evolutionary paths and suggests that some of the complex II enzymes (types A-C) co-evolved as the whole assembly. Origin of complex II types D and F may have arisen from independent events of de novo association of the conserved soluble domain with a new anchor. Here we analyze a recent structure of Mycobacterium smegmatis Sdh2, a complex II enzyme with two transmembrane subunits and two heme b molecules. This analysis supports an earlier hypothesis suggesting that mitochondrial complex II (type C) with a single heme b may have evolved as an assembled unit from an ancestor similar to M. smegmatis Sdh2.

Organocatalyzed Cross-Nucleophile Couplings: Umpolung of Catalytic Enamines.

The concept of umpolung, or polarity reversal, introduced by Seebach and Corey nearly half a century ago, ushered a new paradigm into synthetic chemistry. Novel connections were able to be forged among functional groups that were typically inaccessible. Conceptually, an umpolung reaction is identified only upon retrosynthetic analysis. Stoichiometric examples have served as a platform to develop and refine elegant methodologies into catalytic processes. The advent of these unconventional arrangements of canonical synthons into new points of diversity has expanded the repertoire of the synthetic toolbox. Within this context, asymmetric organocatalyzed methodologies remain rare, and there are even fewer aminocatalyzed variants.Recent years have witnessed a renaissance in α-functionalizations of aldehydes, specifically in the context of oxidative umpolung strategies. Unlike previous open-shell approaches, application of a quinone-based oxidant in conjunction with an aminocatalyst leads to a discrete, substitutionally labile quinone adduct. These have proven to be valuable building blocks toward polar reactivity─auguring the advent of new avenues to construct tetrasubstituted tertiary stereocenters through the application of conventional nucleophiles to form C-C, C-N, C-O, and C-S bonds through an organocatalyzed cross-nucleophile coupling (organo-CNC) reaction. The resulting nonepimerizable stereocenter demonstrates high optical fidelity and provides a significant advancement in many applications that suffer from racemization, such as in vivo studies.This strategy harnesses a trifunctional aminocatalyst to promote an unusual SN2 reaction at a highly congested center. The selection of the quinone oxidant and nucleophile converges to a continuum of reactivity ranging from enantioselective oxidation to stereoselective substitution. A remarkable aspect of these developments is the identification of an asymmetric SN2 dynamic kinetic resolution (SN2-DKR) manifold. These organo-CNC reactions are highly modular and demonstrate complete stereocontrol from the catalyst with minimal influence from incoming chiral nucleophiles. Leveraging this facet, these technologies have been extended to peptidic bioconjugations bearing bio-orthogonoal linker molecules.This Account aims to highlight the progress, from an internal perspective, toward directing the initial result into established methodologies. Within this construct, the underlying principles of each reaction will be disseminated with specific content on inherent challenges and opportunity. Combined, these will serve as an instructive tool to stimulate applications in cross-disciplinary interfaces.

Stability and Optical Absorption of a Comprehensive Virtual Library of Minimal Eumelanin Oligomer Models**

AbstractEumelanin is responsible for photoprotection in living organisms. It is made of 5,6‐dihydroxyindole (DHI) oligomers. However, lack of detailed structural knowledge limits understanding its function and exploiting its potential in material science. To uncover the relationship between structural stability and optical properties, we have studied a virtual library of 830 DHI dimers. We find a preference for oxidized, polycyclic structures which speaks in favor of graphite‐like structures for the larger oligomers, and propose an electrocyclic formation mechanism. Besides widely considered quinone oxidation patterns, also structures with interfragment double bonds and zwitterionic resonance structures are stable. Future theoretical melanine models will have to cover this diversity, and we introduce a new representative set of 49 stable dimers. Some stable oxidized dimers have absorption energies as low as 1.3 eV. They may be present as substructures in the naturally found oligomers and contribute to the absorption spectrum of the biopolymer.

Regiodivergent Isosorbide Acylation by Oxidative N-Heterocyclic Carbene Catalysis in Batch and Continuous Flow

A new N-heterocyclic carbene (NHC)-catalyzed strategy for the regioselective monoesterification of isosorbide (IS) at either the endo (5-OH) or exo (2-OH) position is described. Site-selective acylation proceeds under oxidative conditions in the presence of a quinone oxidant using aldehydes as mild acylating agents. Experimental evidences suggest a role of the stereoelectronic features of the acyl azolium salt intermediate in determining the selectivity of the acylation process. The solvent effect was also investigated, considering conventional and sustainable solvents. Aromatic aldehydes, including bio-based furfural and 5-hydroxymethyl furfural, together with α,β-unsaturated aldehydes proved to be effective reaction partners affording monoacyl-isosorbides with satisfactory levels of regioselectivity (exo/endo: 5.3–3.5; endo/exo: 5.3–3.3). Additionally, the exo-selective triazolium salt promoter was successfully transferred into the heterogeneous phase and applied to continuous-flow catalysis. In particular, the polystyrene-supported version of the selected NHC showed a catalytic activity comparable to that of the homogeneous counterpart in terms of both conversion efficiency (turnover number = 108) and regioselectivity (exo/endo up to 5.3). Also, the corresponding packed-bed mesoreactor was operated with long-term stability (ca. 110 h on stream) to produce 2-benzoyl-IS (1.32 mmol h–1 mmolcat–1), which is the key intermediate in the synthesis of a commercial active pharmaceutical ingredient, namely, the vasodilator isosorbide-5-mononitrate.

705-P: Increasing the Longevity of an Insulin Pump by Removal of Phenolic Excipients within the Cannula through Electrooxidation

Insulin pumps provide an alternative way to conveniently and effectively bring blood glucose level under control. However, insulin pump users often face unexpectable failure of insulin delivery despite the lack of pump occlusions or insulin denaturing. One possible reason for this loss of insulin efficacy is due to phenolic excipients in insulin formulations that can induce cell death and inflammation. Here, we propose an electrochemical method that removes the phenol and m-cresol from insulin to preserve the longevity of the insulin and pump site. To achieve our goal, we modified carbon fiber paper electrodes with polydopamine to increase its hydrophilicity and introduce reaction site. Poly-L-lysine (PLL) was further covalently bound to polydopamine coating, reducing undesirable protein interactions. To reduce electrode passivation and fouling due to phenol deposition on the electrode, we incorporated copper ions to the PLL to form a PLL-Cu complex that mimics the catalytic center of tyrosinase, facilitating the conversion of phenolic compound to a more soluble quinone oxidation product rather than insoluble polyphenols. Figure shows the electrochemical modification scheme as well as cyclic voltammograms and chronoamperometric curves of 30 mM phenol in PBS buffer with 20 mg/mL glycerol on various electrodes at an applied potential of 0.75 or 0.6 V (stirring rate: 1100 min−1). Disclosure S. Pennathur: Employee; Self; Laxmi Therapeutic Devices. L. Zhou: None. F. Lorestani: None. A. Eden: None. D. Huber: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-17-VSN-18 to S.P.)

Exploring Oxidative NHC-Catalysis as Organocatalytic Polymerization Strategy towards Polyamide Oligomers.

The polycondensation of diamines and dialdehydes promoted by an N-heterocyclic carbene (NHC) catalyst in the presence of a quinone oxidant and hexafluoro-2-propanol (HFIP) is herein presented for the synthesis of oligomeric polyamides (PAs), which are obtained with a number-average molecular weight (Mn ) in the range of 1.7-3.6 kg mol-1 as determined by NMR analysis. In particular, the utilization of furanic dialdehyde monomers (2,5-diformylfuran, DFF; 5,5'-[oxybis(methylene)]bis[2-furaldehyde], OBFA) to access known and previously unreported biobased PAs is illustrated. The synthesis of higher molecular weight PAs (poly(decamethylene terephthalamide, PA10T, Mn = 62.8 kg mol-1 ; poly(decamethylene 2,5-furandicarboxylamide, PA10F, Mn = 6.5 kg mol-1 ) by a two-step polycondensation approach is also described. The thermal properties (TGA and DSC analyses) of the synthesized PAs are reported.

Enantioselective N‐Acylation of Biginelli Dihydropyrimidines by Oxidative NHC Catalysis

The oxidative N‐acylation reaction of 3,4‐dihydropyrimidin‐2‐(1H)‐ones (DHPMs) with enals and N‐heterocyclic carbene (NHC) catalysts is described. The reaction proceeds in the presence of quinone oxidant without additional acyl transfer agents and in the asymmetric variant produces pharmaceutically relevant N3‐acylated products with good‐to‐moderate enantioselectivity.

Binding and Reactivity of Copper to R1 and R3 Fragments of tau Protein.

Tau protein is present in significant amounts in neurons, where it contributes to the stabilization of microtubules. Insoluble neurofibrillary tangles of tau are associated with several neurological disorders known as tauopathies, among which is Alzheimer's disease. In neurons, tau binds tubulin through its microtubule binding domain which comprises four imperfect repeats (R1-R4). The histidine residues contained in these fragments are potential binding sites for metal ions and are located close to the regions that drive the formation of amyloid aggregates of tau. In this study, we present a detailed characterization through potentiometric and spectroscopic methods of the binding of copper in both oxidation states to R1 and R3 peptides, which contain one and two histidine residues, respectively. We also evaluate how the redox cycling of copper bound to tau peptides can mediate oxidation that can potentially target exogenous substrates such as neuronal catecholamines. The resulting quinone oxidation products undergo oligomerization and can competitively give post-translational peptide modifications yielding catechol adducts at amino acid residues. The presence of His-His tandem in the R3 peptide strongly influences both the binding of copper and the reactivity of the resulting copper complex. In particular, the presence of the two adjacent histidines makes the copper(I) binding to R3 much stronger than in R1. The copper-R3 complex is also much more active than the copper-R1 complex in promoting oxidative reactions, indicating that the two neighboring histidines activate copper as a catalyst in molecular oxygen activation reactions.

Synthesis of anti-1,3 Amino Alcohol Motifs via Pd(II)/SOX Catalysis with the Capacity for Stereodivergence.

We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33 substrates, avg. 66% isolated yield, >20:1 dr) and high selectivities (avg. 10:1 dr). Switching ligands to (±)-CF3-SOX with the use of a less bulky quinone oxidant, the kinetic syn-1,3 amino alcohol motif can be accessed in comparable yields and selectivities. Advantages of the stereodivergent nature of this reaction are seen in the synthesis of anti- and syn-1,3 amino alcohol vitamin D3 analogue intermediates in half the steps and higher overall yield relative to previous routes. Additionally, all eight possible stereoisomers of a chiral diamino alcohol core are generated from two amino acids. Mechanistic studies reveal that the anti-isomer is furnished through concurrent Pd(II)(SOX) catalyzed C-H amination and Pd(0)(SOX) catalyzed isomerization cycles.

Removal of Linear and Branched Alkylphenols with the Combined Use of Polyphenol Oxidase and Chitosan.

Removal of linear and branched alkylphenols with different alkyl chain lengths or different branchings (normal, secondary, and tertiary), some of which are suspected as endocrine disrupting chemicals, from an aqueous medium were investigated through quinone oxidation by polyphenol oxidase (PPO) and subsequent quinone adsorption on chitosan beads or powders at pH 7.0 and 40 °C. PPO-catalyzed quinone oxidation increased with an increase in alkyl chain length of the alkylphenols used. Although a higher PPO dose was required for quinone oxidation of branched alkylphenols, they were completely or mostly removed by quinone adsorption on chitosan beads or powders. The apparent activity of PPO increased by a decrease in quinone concentration. On the other hand, in the homogeneous systems with solutions of chitosan and PPO at pH 6.0, longer reaction times were required to generate insoluble aggregates, and a small amount of quinone derivatives were left in the solution even under optimum conditions. These results support that the two-step reaction, that is, PPO-catalyzed quinone oxidation and subsequent quinone adsorption on chitosan beads or powders, in the heterogeneous system is a good procedure for removing linear and branched alkylphenols from aqueous medium.

Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis.

The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.

Design of composite microneedle sensor systems for the measurement of transdermal pH

Abstract Carbon loaded polystyrene microneedle patches have been prepared using silicone micro-moulding techniques and the ability of the needles to serve as viable transdermal sensors has been evaluated. The population of quinone groups at the interface of the embedded carbon nanoparticles was increased through anodisation and their pH dependent redox transitions exploited as the basis of a reagentless pH sensor. The peak position of the quinone oxidation process was found to shift in accordance with Nernstian behaviour and the influence of penetration depth on response has been investigated. The analytical applicability of the microneedle electrode patch was critically evaluated through using tomato skin as model transdermal skin mimic. Despite the increased complexity of the matrix, the microneedle sensor response was found to compare favourably with conventional/commercial pH probes.

Unified synthesis and cytotoxic activity of 8-O-methylfusarubin and its analogues.

A simple and unified synthesis of four related pyranonaphthoquinone natural products, e.g. 8-O-methylfusarubin, 8-O-methylanhydrofusarubin, fusarubin and anhydrofusarubin, is reported. The key synthetic features include the precedented Diels-Alder cycloaddition to assemble the naphthalene skeleton, selective formylation and acetonylation and intramolecular acetalization to construct the pyran ring. Manipulation of the oxidation state of the naphthoquinone core was performed to construct the two analogues, fusarubin and anhydrofusarubin. This work also highlights an unprecedented directing effect of the hydroxymethylene group in the selective hypervalent iodine-mediated quinone oxidation. The four synthetic compounds were evaluated for their in vitro cytotoxic activities against six human cancer cells. 8-O-Methylfusarubin was the most potent analogue and displayed excellent cytotoxic activity against MCF-7 breast cancer cells with an IC50 value of 1.01 μM with no cytotoxic effect on noncancerous Vero cells, which could potentially be a promising lead compound for anti-breast cancer drug discovery.