Dual Chemistry Research Articles

N‐Oxyl Radicals in Oxidative C–O Coupling: Free‐Radical Hydrogen Substitution and Addition to C=C Bonds

N‐oxyl radicals occupy an important place in free‐radical oxidative CH‐functionalization being one of the most efficient redox‐organocatalysts for hydrogen atom abstraction (HAT). Their applications include aerobic radical chain autoxidation, CH‐functionalization with the formation of carbon‐carbon and carbon‐heteroatom bonds. The persistent nature of N‐oxyl radicals combined with their high reactivity in HAT results in their unique dual chemistry: the same radical can both propagate radical chain reaction (at low N‐oxyl concentrations) and effectively “terminate” carbon‐centered radicals (at higher N‐oxyl concentrations). The latter case opens a new synthetic application area of N‐oxyl radicals, in which they act as both hydrogen abstracting species and O‐reagents for cross‐coupling with carbon‐centered radicals thus produced. Apart from the C–H bond cleavage, reactive N‐oxyl radicals have been extensively used recently in C=C double bond functionalization via radical addition reactions. In this review, both free‐radical CH‐functionalization reactions with the introduction of N‐oxyl fragments and alkene difunctionalizations by N‐oxyls are covered with emphasis on the relationship between reaction conditions and selectivity.

N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry

Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N-formimidoylation or N-iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.

Highly reversible anode with Bi and ZnO dual chemistry for aqueous alkaline battery

Zn has been recognized as a promising anode material for aqueous alkaline rechargeable batteries (AARBs). However, the further development of Zn anodes suffers from uncontrollable dendrite growth, Zn corrosion and passivation in alkaline electrolyte. To address these issues, we demonstrate a Bi–ZnO hybrid composite as a stable and high-capacity anode for high-energy AARBs. The integration of Bi and ZnO can not only inherit the high capacity and suitable redox potential from ZnO, but also ensure good cycling stability by lowering the Zn nucleation overpotential and boosting the reversibility of Zn plating/stripping. Benefiting from these advantages, the Bi–ZnO anode presents higher Coulombic efficiency than ZnO anode. When employed in AARB, the Bi–ZnO anode also shows impressive durability with 101.6% capacity retention after 2000 cycles, superior to ZnO anode (20.1%). Besides, the Bi–ZnO anode exhibits a high capacity (238 mAh g−1) and energy density (214 Wh kg−1). Moreover, the reaction mechanism of Bi–ZnO anode is proved to be Bi/Bi3+ redox reaction and Zn/Zn2+ stripping/plating reaction.

Architectural design of core-shell nanotube systems based on aluminosilicate clay.

A nanoarchitectural approach to the design of functional nanomaterials based on natural aluminosilicate nanotubes and their catalysis, and practical applications are described in this paper. We focused on the buildup of hybrid core–shell systems with metallic or organic molecules encased in aluminosilicate walls, and nanotube templates for structured silica and zeolite preparation. The basis for such an architectural design is a unique Al2O3/SiO2 dual chemistry of 50 nm diameter halloysite tubes. Their structure and site dependent properties are well combined with biocompatibility, environmental safety, and abundant availability, which makes the described functional systems scalable for industrial applications. In these organic/ceramic hetero systems, we outline drug, dye and chemical inhibitor loading inside the clay nanotubes, accomplished with their silane or amphiphile molecule surface modifications. For metal–ceramic tubule composites, we detailed the encapsulation of 2–5 nm Au, Ru, Pt, and Ag particles, Ni and Co oxides, NiMo, and quantum dots of CdZn sulfides into the lumens or their attachment at the outside surface. These metal–clay core–shell nanosystems show high catalytic efficiency with increased mechanical and temperature stabilities. The combination of halloysite nanotubes with mesoporous MCM-41 silica allowed for a synergetic enhancement of catalysis properties. Finally, we outlined the clay nanotubes’ self-assembly into organized arrays with orientation and ordering similar to nematic liquid crystals, and these systems are applicable for life-related applications, such as petroleum spill bioremediation, antimicrobial protection, wound healing, and human hair coloring.

Controlled Water Uptake in Fuel Cell Membranes with Dual Chemistry Confinement

Nafion is one of the most commonly used materials for proton exchange membranes in polymer-electrolyte fuel cells (PEFC) due to its stability and high ion-transport capabilities. However, its dehydration problem as well as dimensional instability limits its application in high-temperature, low-humidity environments. In this paper, we propose a potential solution to this problem by introducing nanoscale confinements to the Nafion chains. In particular, a coarse grain molecular dynamics model is developed that reproduces the water absorption curve of the pristine Nafion membrane. The model enables us to perform systematic studies on the effects of confinement to the absorption behavior of the Nafion membrane at different activities. Confinement of different chemistries and sizes has been introduced in the simulation system in order to investigate its effects on water absorption on different activities. It is found that confinement of dual chemistry (consisting of both hydrophobic and hydrophilic confinements) offers a solution to its drawbacks. The hydrophobic confinement helps flatten the absorption curve and decrease the water absorption at high activity, while the hydrophilic confinement acts as a water reservoir, which increases the water absorption at low activity. The Nafion membrane with dual chemistry confinement in general has higher water absorption with smaller dimensional instability, which makes it suitable to operate in a high-temperature, low-humidity environment.

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials.

Peptides are of continued interest for therapeutic applications, from soluble and immobilized ligands that promote desired binding or uptake to self-assembled supramolecular structures that serve as scaffolds in vitro and in vivo. These applications require efficient and scalable synthetic approaches because of the large amounts of material that often are needed for studies of bulk material properties and their translation. In this work, we establish new methods for the synthesis, purification, and visualization of assembling peptides, with a focus on multifunctional collagen mimetic peptides (mfCMPs) relevant for formation and integration within hydrogel-based biomaterials. First, a methodical approach useful for the microwave-assisted synthesis of assembling peptide sequences prone to deletions was established, beginning with the identification of the deleted residues and their locations and followed by targeted use of dual chemistry couplings for those specific residues. Second, purification techniques that integrate the principles of heating and ion displacement with traditional chromatography and dialysis were implemented to improve separation and isolation of the desired multifunctional peptide product, which contained blocks for thermoresponsiveness and ionic interactions. Third, an approach for fluorescent labeling of these mfCMPs, which is orthogonal to their assembly and their covalent incorporation into a bulk hydrogel material, was established, allowing visualization of the resulting hierarchical fibrillar structures in three dimensions within hydrogels using confocal microscopy. The methods presented in this work allow the production of multifunctional peptides in scalable quantities and with minimal deletions, enabling future studies for better understanding of composition-structure-property relationships and for translating these biomaterials into a range of applications. Although mfCMPs are the focus of this work, the methods demonstrated could prove useful for other assembling peptide systems and for the production of peptides more broadly for therapeutic applications.

Electron Beam Lithography Nanopatterning of Plasma Polymers

AbstractChemically patterned surfaces for biotechnology applications often require sub‐micron patterns to match specific sub‐cellular structures and control the presentation of proteins to single cell arrays. Plasma polymer coatings are used extensively in the biotechnology sector for biomaterials, cell culture and tissue engineering, but their patterning has not been investigated at the sub‐micron level. The resolution limit of plasma polymerized patterns with designed line widths of 900 to 20 nm is investigated via dual chemistry patterns of plasma polymerized acrylic acid and allylamine created with poly (methyl methacrylate) resist and electron beam lithography (EBL). Line widths are characterized via scanning electron microscopy and atomic force microscopy with surface chemistry analysis via time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). The smallest line width measured is 29 nm for a designed line width of 20 nm. High‐resolution nanoscale imaging is achieved using ToF‐SIMS, with lines down to ≈60 nm in width visible. This work demonstrates the successful fabrication and characterization of sub 100 nm dual plasma polymer patterns using EBL, establishing a clear route for large scale production of plasma polymerized nanopatterning.

Synthesis of Chromone-Related Pyrazole Compounds.

Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century.

The Metal Drives the Chemistry: Dual Functions of Acireductone Dioxygenase.

Acireductone dioxygenase (ARD) from the methionine salvage pathway (MSP) is a unique enzyme that exhibits dual chemistry determined solely by the identity of the divalent transition-metal ion (Fe2+ or Ni2+) in the active site. The Fe2+-containing isozyme catalyzes the on-pathway reaction using substrates 1,2-dihydroxy-3-keto-5-methylthiopent-1-ene (acireductone) and dioxygen to generate formate and the ketoacid precursor of methionine, 2-keto-4-methylthiobutyrate, whereas the Ni2+-containing isozyme catalyzes an off-pathway shunt with the same substrates, generating methylthiopropionate, carbon monoxide, and formate. The dual chemistry of ARD was originally discovered in the bacterium Klebsiella oxytoca, but it has recently been shown that mammalian ARD enzymes (mouse and human) are also capable of catalyzing metal-dependent dual chemistry in vitro. This is particularly interesting, since carbon monoxide, one of the products of off-pathway reaction, has been identified as an antiapoptotic molecule in mammals. In addition, several biochemical and genetic studies have indicated an inhibitory role of human ARD in cancer. This comprehensive review describes the biochemical and structural characterization of the ARD family, the proposed experimental and theoretical approaches to establishing mechanisms for the dual chemistry, insights into the mechanism based on comparison with structurally and functionally similar enzymes, and the applications of this research to the field of artificial metalloenzymes and synthetic biology.

Dual chemistry catalyzed by human acireductone dioxygenase.

Acireductone dioxygenase (ARD) from the methionine salvage pathway of Klebsiella oxytoca is the only known naturally occurring metalloenzyme that catalyzes different reactions in vivo based solely on the identity of the divalent transition metal ion (Fe2+ or Ni2+) bound in the active site. The iron-containing isozyme catalyzes the cleavage of substrate 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, whereas the nickel-containing isozyme uses the same substrates to catalyze an off-pathway shunt to form methylthiopropionate, carbon monoxide and formate. This dual chemistry was recently demonstrated in vitro by ARD from Mus musculus (MmARD), providing the first example of a mammalian ARD exhibiting metal-dependent catalysis. We now show that human ARD (HsARD) is also capable of metal-dependent dual chemistry. Recombinant HsARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. As with MmARD, the Fe2+-bound HsARD shows the highest activity and catalyzes on-pathway chemistry, whereas Ni2+, Co2+ or Mn2+ forms catalyze off-pathway chemistry. The thermal stability of the HsARD isozymes is a function of the metal ion identity, with Ni2+-bound HsARD being the most stable followed by Co2+ and Fe2+, and Mn2+-bound HsARD being the least stable. As with the bacterial ARD, solution NMR data suggest that HsARD isozymes can have significant structural differences depending upon the metal ion bound.

Metal-Dependent Function of a Mammalian Acireductone Dioxygenase.

The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate the metal ion identity and three-dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, which is the penultimate step in methionine salvage. The nickel-bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO), and 3-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe(2+)-bound protein, which shows about 10-fold higher activity than that of others, catalyzes on-pathway chemistry, whereas the Ni(2+), Co(2+), or Mn(2+) forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by the metal ion identity, with Ni(2+)-bound MmARD being the most stable, followed by Co(2+) and Fe(2+), and Mn(2+)-bound ARD being the least stable. Ni(2+)- and Co(2+)-bound MmARD were crystallized, and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination, and the catalytic mechanism.

Witnessing the emergence of a carbon star

Abstract During the late stages of their evolution, Sun-like stars bring the products of nuclear burning to the surface. Most of the carbon in the Universe is believed to originate from stars with masses up to a few solar masses. Although there is a chemical dichotomy between oxygen-rich and carbon-rich evolved stars, the dredge-up itself has never been directly observed. In the last three decades, however, a few stars have been shown to display both carbon- and oxygen-rich material in their circumstellar envelopes. Two models have been proposed to explain this dual chemistry: one postulates that a recent dredge-up of carbon produced by nucleosynthesis inside the star during the Asymptotic Giant Branch changed the surface chemistry of the star. The other model postulates that oxygen-rich material exists in stable keplerian rotation around the central star. The two models make contradictory, testable, predictions on the location of the oxygen-rich material, either located further from the star than the carbon-rich gas, or very close to the star in a stable disc. Using the Faint Object InfraRed CAmera (FORCAST) instrument on board the Stratospheric Observatory for Infrared Astronomy (SOFIA) Telescope, we obtained images of the carbon-rich planetary nebula BD +30° 3639 which trace both carbon-rich polycyclic aromatic hydrocarbons and oxygen-rich silicate dust. With the superior spectral coverage of SOFIA, and using a 3D photoionization and dust radiative transfer model we prove that the O-rich material is distributed in a shell in the outer parts of the nebula, while the C-rich material is located in the inner parts of the nebula. These observations combined with the model, suggest a recent change in stellar surface composition for the double chemistry in this object. This is evidence for dredge-up occurring ∼103 yr ago.

Simultaneous dehydration of biomass-derived sugars to 5-hydroxymethyl furfural (HMF) and reduction of graphene oxide in ethyl lactate: one pot dual chemistry

Biomass-based sugars were dehydrated in ethyl lactate in the presence of graphene oxide, choline chloride and betaine hydrochloride resulting in the formation of HMF and rGO.

Measurement of plasma 5-hydroxyindole acetic acid by liquid chromatography tandem mass spectrometry—Comparison with HPLC methodology

In patients with carcinoid disease, urinary concentration of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) is currently used to monitor disease progression or response to treatment as it is the metabolic end-product resulting from free and stored serotonin turnover. However, due to the undignified, cumbersome and error-prone nature of 24-h urine collections, there is constant pressure to replace them. It has been demonstrated using high performance liquid chromatography (HPLC) with fluorescence detection technology that plasma can achieve this, with the added advantage that it can be used for diagnostic purposes also. Here we describe a much simpler method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) that is twice as fast as a HPLC method currently in routine use. The sample preparation protocol requires 50 μL of plasma and a simple protein precipitation step facilitated by acetonitrile. Chromatography was performed on a Phenomenex C18 Security Guard™ column coupled to a SIELC Primesep B reversed-phase, anion-exchange dual chemistry column and methanolic mobile phase gradient elution. Eluant was directly connected to a Waters ® Quattro Premier™ XE tandem mass spectrometer operating in positive ion mode. We detected multiple reaction monitoring transitions m/ z 191.9 > 145.6 and 193.9 > 147.6 for 5-HIAA and d2-5-HIAA respectively, which co-eluted at 2.1 min. Ion suppression was negligible, recovery from spiked plasma was 103% (range 97–113%) and the method showed good linearity to 10,000 nmol/L ( r 2 = 0.999). Within-batch and between-batch imprecision was <10% and bias <15% at 3 concentrations, the limit of detection was 5 nmol/L and lower limit of quantitation 15 nmol/L. No interference was observed with l-tryptophan or 5-hydroxytryptamine. Comparison of LC–MS/MS and HPLC showed good agreement between the two methods but this LC–MS/MS assay displays several advantages; it requires 10-fold less sample, has a simpler extraction procedure and extended linearity, thus increasing laboratory throughput, lowering reagent costs and removing the need to dilute samples in patients with established carcinoid disease being monitored for therapeutic efficacy.

Chemical Abundances and Dust in Planetary Nebulae in the Galactic Bulge

We present mid-infrared Spitzer spectra of eleven planetary nebulae in the Galactic Bulge. We derive argon, neon, sulfur, and oxygen abundances for them using mainly infrared line fluxes combined with some optical line fluxes from the literature. Due to the high extinction toward the Bulge, the infrared spectra allow us to determine abundances for certain elements more accurately that previously possible with optical data alone. Abundances of argon and sulfur (and in most cases neon and oxygen) in planetary nebulae in the Bulge give the abundances of the interstellar medium at the time their progenitor stars formed; thus these abundances give information about the formation and evolution of the Bulge. The abundances of Bulge planetary nebulae tend to be slightly higher than those in the Disk on average, but they do not follow the trend of the Disk planetary nebulae, thus confirming the difference between Bulge and Disk evolution. Additionally, the Bulge planetary nebulae show peculiar dust properties compared to the Disk nebulae. Oxygen-rich dust feature (crystalline silicates) dominate the spectra of all of the Bulge planetary nebulae; such features are more scarce in Disk nebulae. Additionally, carbon-rich dust features (polycyclic aromatic hydrocarbons) appear in roughly half of the Bulge planetary nebulae in our sample, which is interesting in light of the fact that this dual chemistry is comparatively rare in the Milky Way as a whole.

About the nature of IRAS 19075+0921

We use infrared data to further investigate the nature of IRAS 19075+0921. Our results indicate that IRAS 19075+0921 is heavily obscured by its thick, circumstellar envelope and possibly composed of two infrared sources all with late spectral types so that it presents a dual chemistry nature.