Dimeric Products Research Articles

Porous N-Doped Carbon-encapsulated Iron as Novel Catalyst Architecture for the Electrocatalytic Hydrogenation of Benzaldehyde.

Carbon porous materials containing nitrogen functionalities and encapsulated iron-based active sites have been suggested as electrocatalysts for energy conversion, however their applications to the hydrogenation of organic substrates via electrocatalytic hydrogenation (ECH) remain unexplored. Herein, we report on a Fe@C:N material synthesized with an adapted annealing procedure and tested as electrocatalyst for the hydrogenation of benzaldehyde. Using different concentrations of the organic, and electrolysis coupled to gas chromatography experiments, we demonstrate that it is possible to use such architectures for the ECH of unsaturated organics. Potential control experiments show that ECH faradaic efficiencies >70 % are possible in acid electrolytes, while maintaining selectivity for the alcohol over the pinacol dimerization product. Estimates of product formation rates and turnover frequency (TOF) values suggest that these carbon-encapsulated architectures can achieve competitive performance in acid electrolytes relative to both base and precious metal electrodes.

Renormalization of three-body interaction in DDK system

In systems comprising three identical particles, the Efimov effect emerges in the unitary limit. This article, utilizing the method of effective field theory along with the effective range expansion (ERE) and low-momentum expansion, reproduces the Efimov effect beyond unitary limit and identical case and applies to DDK system. It also links the high-energy scale with the ultraviolet cutoff in the three-body system. We discuss a method for obtaining exact solutions for the three-body wave function below the threshold of dimer production, that is D and Ds0⁎(2317). It turns out that introducing this scale is a necessary condition for the emergence of DDK three-body bound state. Since without this scale, the wave function would be solved below threshold with arbitrary binding energy, which violates the conditions of unitarity and energy quantization. The calculation involving this scale results in a discrete spectrum below the threshold and restores unitarity, making the effects induced by this scale significant for the formation of DDK bound state. In order to establish this in a complete formalism, the paper further gives an analytical expression for the three-body coupling constant, and compares it to the numerical calculation in DDK system.

Chiral Peropyrene by Selective Dimerization of Phenalenyl.

Two aryl substituted phenalenyl derivatives were synthesized, providing an opportunity to study the steric effects on selectivity of phenalenyl dimerization. Owing to σ-dimerization serving as the decisive step in phenalenyl-peropyrene transformation, a chiral peropyrene compound was generated by dimerization of triarylphenalenyl, while tetraarylphenalenyl did not afford any dimerized product. The structure and properties of chiral peropyrene were elaborated. Our study showcases that phenalenyl dimerization could function as a useful tool to synthesize fascinating π-conjugated hydrocarbons.

Whole-Cell Biotransformation for the Preparation of Chromopyrrolic Acid and 5,5'-dichloro-Chromopyrrolic Acid in Escherichia coli.

Chromopyrrolic acid (CPA) and its congeners are important intermediates for the biosynthesis and synthesis of various dimeric tryptophan natural products. We have constructed two E. coli strains (CPA001/CPA002) harboring a single plasmid carrying genes coding for a combination of two enzymes (LaStaO/LzrO and VioB) that are able to convert L-tryptophan (L-Trp)/5-chloro-L-tryotophan (5-Cl-L-Trp) to chromopyrrolic acid (CPA)/5,5'-dichloro-chromopyrrolic acid (5,5'-diCl-CPA). Effect on the production of CPA were evaluated by varying the parameters of strain cultivation and biotransformation process. Under the optimized conditions, up to 325 mg/L of CPA and 275 mg/L of 5,5'-diCl-CPA could be obtained by supplementing L-Trp and 5-Cl-L-Trp, respectively, to a working culture of CPA001, or to a phosphate buffer-resuspended culture of CPA002. The practicability of this whole-cell biotransformation system could also be served as a potential platform for the preparation of CPA congeners.

Dimeric natural product panepocyclinol A inhibits STAT3 via di-covalent modification

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Dimerization of perfluoropropyl vinyl ether during the pyrolysis of hexafluoropropylene oxide dimer

Dimerization of perfluoropropyl vinyl ether (PPVE) generally reduces its yield and selectivity during the pyrolysis of hexafluoropropylene oxide dimer ((HFPO)2). However, the mechanism of PPVE dimerization is not well understood. In this paper, the PPVE dimer was obtained during the pyrolysis of (HFPO)2. Subsequently, the chemical structure of PPVE dimer was further determined by gas chromatography-mass spectrometry (GC–MS) and nuclear magnetic resonance (NMR). The results showed that the concentration of PPVE dimer rises in proportion to the extended reflux time of PPVE in the reaction system. Based on the experimental phenomenon, a possible generation mechanism of PPVE dimer was then proposed, and the possibility of the generation pathway was further verified in combination with density functional theory (DFT). In addition, to effectively reduce the production of PPVE dimer, crown ethers and quaternary ammonium salts were added to the reaction system as phase transfer catalysts. Among them, the phase transfer catalyst (15-crown-5) was more effective and reduced the PPVE dimer content from 1.34 % to 0.31 %. This work provides an idea to inhibit the dimerization of PPVE and increase the yield and selectivity of PPVE.

Photochemical Dimerization of Indones: A DFT Study

In this study, DFT calculations were performed in order to identify the reaction products of the photochemical dimerization of indones. Calculations allowed us to assume that all tested reactions occurred in the first excited singlet state. The irradiation of 2-phenyl-5-nitroindone gave the main product, the <i>anti-cis</i> head-to-tail dimer, while the other two compounds found in the experiments were the <i>syn-cis</i> head-to-head dimer and the <i>anti-cis</i> head-to-tail dimer. The irradiation of 2-phenylindone gave the main product, <i>syn-cis</i>-head-to-tail dimer, while the minor products were <i>anti-cis</i>-head-to-tail and <i>anti-cis</i>-head-to-head dimer. The photochemical dimerization of 2-methyl-3-phenylindone gave the main product, <i>anti-cis</i>-head-to-tail dimer, while the minor component of the mixture was <i>syn-cis</i>-head- to-head dimer.

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

A concise synthetic strategy utilizing a Zr‐catalyst for the construction of cyctetryptomycin A and B is herein reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers via a Zr‐catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr‐catalyzed radical coupling. The radical dimerization reaction mediated by the Zr‐catalyst required dppe as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr‐catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr-Catalyzed Dimerization.

A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers via a Zr-catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr-catalyst required dppe as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Janus Reactivity of Crownphyrinoids: Alkali- vs. Transition Metal-Mediated Transformations of Crown Ether-Porphyrin Hybrids.

Crownphyrinogens and crownphyrins constitute a group of macrocycles that combine the structural facets of porphyrinoids and crown ethers. The dual-nature cavity embedded in their molecules enables reactivity involving two structurally distinct parts of the macrocyclic ligand. Upon Ni(II) and Pd(II) insertion, coordination compounds are produced wherein the metal is incorporated into the porphyrinoid-like pocket, resulting in monomeric or accordion-like dimeric products, depending on the oxidation level of the macrocycle and metal cation. The reactions with Na(I) and K(I) resulted in the formation of complexes where only the crown ether segment of the molecule is involved in metal binding, yielding remarkable dimeric species. The exploitation of a crownphyrin large enough to accommodate two metal cations allowed the synthesis of an alkali/transition metal binuclear complexes wherein the macrocycle demonstrated the Janus reactivity with one cavity acting as a porphyrinoid, and the other mimicking the crown ether.

Dry Heating of Curcumin in the Presence of Basic Salts Yields Anti-inflammatory Dimerization Products.

Curcumin exerts some of its biological effects via degradation products formed by spontaneous oxidation at physiological, i.e., weakly basic, pH. Here, we analyzed products formed by dry heating of curcumin in the presence of a basic salt (sodium bicarbonate and others). Under the dry heating conditions employed, curcumin was completely consumed, yielding products entirely different from those obtained by autoxidative degradation in buffer. Bioassay-guided fractionation of the reaction mixture was used to identify and isolate compounds with anti-inflammatory activity in a cell-based assay. This provided two dimers of curcumin, dicurmins A and B, featuring a partly saturated naphthalene core that inhibited lipopolysaccharide-induced activation of NF-κB in RAW264.7 cells. Dicurmin A and B are unusual derivatives of curcumin lacking key functional moieties yet exhibit increased anti-inflammatory activity. The process of dry heating of polyphenols in the presence of a basic salt can serve as a novel approach to generating bioactive compounds.

Dye‐based recombinase‐aided amplification assay with enhanced sensitivity and specificity

AbstractObjectiveFluorescent recombinase‐aided amplification (RAA) assays are increasingly being used in the detection of a variety of pathogens and have the advantages of rapidity and simplicity and similar sensitivity and specificity, compared with real‐time PCR (qPCR) assays, but they require a complex probe design. To eliminate the addition of fluorescent probes for RAA, an EvaGreen dye‐based recombinase‐aided amplification (EvaGreen‐RAA) assay using self‐avoiding molecular recognition system (SAMRS) primers was developed.MethodsThe SAMRS primers effectively avoided the production of primer dimers, thus improving the detection sensitivity, while EvaGreen dye was used to quantitatively measure the amplified products in real time. Using Staphylococcus aureus (SA) and Listeria monocytogenes (LM) as examples, EvaGreen‐RAA with SAMRS primers was developed. As a reference and comparison, a traditional fluorescence probe RAA method and a RAA with SAMRS primers (SAMRS‐RAA) for detecting SA and LM were also investigated. Serial dilutions of recombinant plasmids were used to evaluate the sensitivity of the assays. Unenriched and enriched simulated milk samples were used to evaluate the limits of detection (LOD) of these methods. Using high‐resolution melting (HRM) was used to explore the sensitivity of the dual EvaGreen‐RAA assay.ResultsThe sensitivity of the fluorescent RAA method for detecting SA and LM was 10 copies/μL using plasmids and the sensitivity of the SAMRS‐RAA and EvaGreen‐RAA for detecting SA and LM plasmids was 1 copies/μL. The LOD values of the EvaGreen‐RAA for SA and LM in unenriched simulated milk samples were 100 and 50 CFU/mL, respectively, and the LOD value for both SA and LM using enriched simulated milk samples was 10 CFU/mL. EvaGreen‐RAA had linear amplification in real time in the range of 1–105 copies/μL of the plasmids of SA and LM. The sensitivity of the dual EvaGreen‐RAA assay for SA and LM was estimated to be 102 CFU/mL.ConclusionA real‐time quantitative EvaGreen‐RAA method for detecting SA and LM was developed, which eliminates the need to design complex RAA probes. This dye‐based RAA with SARMS primers provides a new strategy for simplifying fluorescence probe RAA and allowing the detection of multiple pathogens, which has many potential applications.

Generation of pyridinylethylidenemalononitrile cyclic dimer: A facile route to multi-stimuli-responsive far-red/NIR luminogens

A simple synthetic strategy was successfully employed to develop NIR luminophores with switchable color-contrasting luminescence properties. D-A molecular motifs with dicyanovinylene appended pyridinyl moiety as the electron-withdrawing unit was not reported among luminescent molecules so far, owing to its unstable precursor compound pyridinylethylidenemalononitrile. By modifying the Knoevenagel condensation reaction pathways, the present work succeeded for the first time in identifying and crystallizing a novel cyclic dimerization product of the precursor compound. It further reports a new, simple, efficient synthetic route to achieve push-pull far-red/NIR emissive luminophores with the dicyanovinylene appended pyridinyl skeleton as the potent electron withdrawing unit. The enhanced charge transfer and the acidochromic characteristics make them suitable candidates in multi-stimuli-responsive smart materials with anti-counterfeiting applications.

Platinum-Catalyzed Hydrative Dimerization of Alkynylsilanes to α,β-Unsaturated Ketones.

A unique type of platinum catalysis that is valuable for the synthesis of α,β-unsaturated ketones is described. In the presence of PtCl2, (2-arylethynyl)trimethylsilanes reacted with H2O at 30 °C to give 1,4-diarylbut-3-en-2-ones in moderate to good yields. (2-Alkylethynyl)trimethylsilanes could be efficiently converted into the corresponding hydrative dimerization products by a modified Pt catalyst system. Mechanistic studies suggest the participation of acylplatinum intermediates in the catalytic cycle.

A General Synthetic Strategy toward the Truxillate Natural Products via Solid-State Photocycloadditions.

The truxillates constitute a large class of dimeric natural products featuring a central, highly substituted cyclobutane core. In principle, these structures could be efficiently synthesized via [2 + 2] photocycloaddition. However, the difficulty in controlling the high-energy electronically excited reactive intermediates in the solution state can lead to poor regio- and diastereocontrol. This has limited the use of photocycloaddition methodology toward the synthesis of this important class of natural products. Herein, we demonstrate that acid-controlled precipitation of C-acyl imidazoles promotes a highly selective solid-state photocycloaddition, and the products of this reaction can be quickly transformed into truxillate natural products.

FGF21 overexpression alleviates VSMC senescence in diabetic mice by modulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway.

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with progressive senescence in vascular smooth muscle cells (VSMCs). The vascular protective effect of FGF21 has gradually gained increasing attention, but its role in diabetes-induced vascular senescence needs further investigation. In this study, diabetic mice and primary VSMCs are transfected with an FGF21 activation plasmid and treated with a peroxisome proliferator-activated receptor γ (PPARγ) agonist (rosiglitazone), an NLRP3 inhibitor (MCC950), and a spleen tyrosine kinase (SYK)-specific inhibitor, R406, to detect senescence-associated markers. We find that FGF21 overexpression significantly restores the level of catalase (CAT), vascular relaxation, inhibits the intensity of ROSgreen fluorescence and p21 immunofluorescence, and reduces the area of SA-β-gal staining and collagen deposition in the aortas of diabetic mice. FGF21 overexpression restores CAT, inhibits the expression of p21, and limits the area of SA-β-gal staining in VSMCs under high glucose conditions. Mechanistically, FGF21 inhibits SYK phosphorylation, the production of the NLRP3 dimer, the expression of NLRP3, and the colocalization of NLRP3 with PYCARD (ASC), as well as NLRP3 with caspase-1, to reverse the cleavage of PPARγ, preserve CAT levels, suppress ROSgreen density, and reduce the expression of p21 in VSMCs under high glucose conditions. Our results suggest that FGF21 alleviates vascular senescence by regulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway in diabetic mice.

Classical vs. quantum plasmon-induced molecular transformations at metallic nanojunctions

Chemical transformations near plasmonic metals have attracted increasing attention in the past few years. Specifically, reactions occurring within plasmonic nanojunctions that can be detected via surface and tip-enhanced Raman (SER and TER) scattering were the focus of numerous reports. In this context, even though the transition between localized and nonlocal (quantum) plasmons at nanojunctions is documented, its implications on plasmonic chemistry remain poorly understood. We explore the latter through AFM-TER-current measurements. We use two molecules: i) 4-mercaptobenzonitrile (MBN) that reports on the (non)local fields and ii) 4-nitrothiophenol (NTP) that features defined signatures of its neutral/anionic forms and dimer product, 4,4'-dimercaptoazobenzene (DMAB). The transition from classical to quantum plasmons is established through our optical measurements: It is marked by molecular charging and optical rectification. Simultaneously recorded force and current measurements support our assignments. In the case of NTP, we observe the parent and DMAB product beneath the probe in the classical regime. Further reducing the gap leads to the collapse of DMAB to form NTP anions. The process is reversible: Anions subsequently recombine into DMAB. Our results have significant implications for AFM-based TER measurements and their analysis, beyond the scope of this work. In effect, when precise control over the junction is not possible (e.g., in SER and ambient TER), both classical and quantum plasmons need to be considered in the analysis of plasmonic reactions.

Carbazole Based Smaragdyrins: Synthesis, Aromaticity Switching, and Formation of a Spiro-Dimer.

Carbazole-incorporated smaragdyrin BF2-complex 3 was synthesized by SNAr reaction of 3,5-dibromo-8-mesityl-BODIPY 1 with 3,6-di(tert-butyl)-1,8-di(pyrrol-2-yl)carbazole 2 as a nucleophile. Demetalation of 3 with ZrCl4 gave the corresponding smaragdyrin free base 4 in a good yield. Oxidations of 3 and 4 with MnO2 gave smaragdyrins 5 and 6, respectively, both followed by aromaticity switching, since the oxidized products showed a moderate paratropic ring current owing to their 20π-electronic circuits. Further, treatment of 4 with [RhCl(CO)2]2 in the presence of NaOAc gave RhI complex 7, and oxidation of 3 with RuCl3 in the presence of triethylamine led to the formation of a spiro dimer product, 8.

Enhancement of the biological activity of hydroxytyrosol through its oxidation by laccase from Trametes versicolor

The laccase-catalyzed oxidation of hydroxytyrosol (HT) towards the formation of its bioactive oligomer derivatives was investigated. The biocatalytic oligomerization was catalyzed by laccase from Trametes versicolor in aqueous or various water-miscible organic solvents and deep eutectic solvent (DES)-based media. Mass Spectroscopy and Nuclear Magnetic Resonance were used for the characterization of the products. The solvent system used significantly affects the degree of HT oligomerization. The use of 50 % v/v methanol favored the production of the HT dimer, while other organic solvents as well as DESs led to the formation of hydroxytyrosol trimer and other oligomers. In vitro studies showed that the HT dimer exhibits 3- to 4-fold enhanced antibacterial activity against Gram-positive and Gram-negative bacteria compared to the parent compound. Moreover, the ability of HT dimer to inhibit the activity of soybean lipoxygenase and Candida rugosa lipase was 1.5-fold higher than HT, while molecular docking supported these results. Furthermore, HT dimer showed reduced cytotoxicity against HEK293 cells and exhibited a strong ability to inhibit ROS formation. The enhanced bioactivity of HT dimer indicates that this compound could be considered for use in cosmetics, skin-care products, and nutraceuticals.

Oxygenated organic molecules produced by low-NOx photooxidation of aromatic compounds: contributions to secondary organic aerosol and steric hindrance

Abstract. Oxygenated organic molecules (OOMs) produced by the oxidation of aromatic compounds are key components of secondary organic aerosol (SOA) in urban environments. The steric effects of substitutions and rings and the role of key reaction pathways in altering the OOM distributions remain unclear because of the lack of systematic multi-precursor study over a wide range of OH exposure. In this study, we conducted flow-tube experiments and used the nitrate adduct time-of-flight chemical ionization mass spectrometer (NO3--TOF-CIMS) to measure the OOMs produced by the photooxidation of six key aromatic precursors under low-NOx conditions. For single aromatic precursors, the detected OOM peak clusters show an oxygen atom difference of one or two, indicating the involvement of multi-step auto-oxidation and alkoxy radical pathways. Multi-generation OH oxidation is needed to explain the diverse hydrogen numbers in the observed formulae. In particular, for double-ring precursors at higher OH exposure, multi-generation OH oxidation may have significantly enriched the dimer formulae. The results suggest that methyl substitutions in precursor lead to less fragmented OOM products, while the double-ring structure corresponds to less efficient formation of closed-shell monomeric and dimeric products, both highlighting significant steric effects of precursor molecular structure on the OOM formation. Naphthalene-derived OOMs however have lower volatilities and greater SOA contributions than the other-type of OOMs, which may be more important in initial particle growth. Overall, the OOMs identified by the NO3--TOF-CIMS may have contributed up to 30.0 % of the measured SOA mass, suggesting significant mass contributions of less oxygenated, undetected semi-volatile products. Our results highlight the key roles of progressive OH oxidation, methyl substitution and ring structure in the OOM formation from aromatic precursors, which need to be considered in future model developments to improve the model performance for organic aerosol.