Classical Reaction Research Articles

Isocyanide-Based Multicomponent Reaction: Cascade α-Acyloxylation/Carboxamidation and [3 + 1+1] Cyclization of I(III)/S(VI)-Ylides.

A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.

Thorium Cluster Synthesized by a Solvent-Free Flux Approach: The Richest Coordination Diversity and Application Exploration.

The renaissance of research interests in actinide oxo clusters in the past decade arises from both the concerns of radioactive contamination and their potential utility as nanoscale materials. Compared to the uranium cluster, the thorium (Th) cluster shows less coordination variation. Herein, we presented a unique Th cluster (ThC-1) that exhibits the most diverse coordination chemistry found within a single Th cluster via a solvent-free flux synthesis approach. The melt triazole not only offers a unique solvation environment that may be responsible for the coordination diversity in ThC-1 but also represents the first nitrogen-donor capping ligand in Th clusters. The potential utility of ThC-1 as a heterogeneous catalyst was also explored for a classical CO2 cycloaddition reaction. This work offers a novel approach in synthesizing Th clusters, broadening the realm of the structural diversity of Th.

Manganese-Mediated Electrochemical Oxidation of Thioethers to Sulfoxides Using Water as the Source of Oxygen Atoms.

Oxygen-atom transfer reactions are a prominent class of synthetic redox reactions that often use high-energy oxygen-atom donor reagents. Electrochemical methods can bypass these reagents by using water as the source of oxygen atoms through pathways involving direct or indirect (mediated) electrolysis. Here, manganese porphyrins and related mediators are shown to be effective molecular electrocatalysts for selective oxidation of thioethers to sulfoxides, without overoxidation to the sulfone. The reactions proceed by proton-coupled oxidation of a MnIII-OH2 species to generate a MnIV-OH and MnV═O species. This methodology is compared to direct electrolysis methods initiated by single-electron oxidation of the thioether, and chloride-mediated electrochemical oxidation of thioethers. The Mn-mediated reactions operate at lower applied potential and exhibit improved substrate scope and functional group compatibility relative to direct electrolysis, and the tunability of the Mn-based mediators allows for improved performance relative to chloride-mediated electrolysis. An electrochemical parallel screening platform is developed and applied to a library of pharmaceutically relevant thioethers.

Coupled X-ray Absorption/UV-vis Monitoring of a Prototypical Oscillating Reaction.

Oscillating reactions are among the most intriguing phenomena in chemistry, but many questions on their mechanisms still remain unanswered, due to their intrinsic complexity and to the low sensitivity of the most common spectroscopic techniques toward the reaction brominated species. In this work, we investigate the cerium ion-catalyzed Belousov-Zhabotinsky (BZ) oscillating reaction by means of time-resolved X-ray absorption spectroscopy (XAS), in combination with UV-vis spectroscopy and unsupervised machine learning, multivariate curve resolution, and kinetic analyses. Altogether, we provide new insights into the collective oscillatory behavior of the key brominated species involved in the classical BZ reaction and measure previously unreported oscillations in their concentrations through Br K-edge XAS, while simultaneously tracking the oscillatory Ce4+-to-Ce3+ transformation by coupling XAS with UV-vis spectroscopy. Our work evidences the potential of the XAS technique to investigate the mechanisms of oscillatory chemical systems whose species are often not detectable with conventional experimental methods.

Automated Skeleton Network Generation for ReaxFF Molecular Dynamics Simulations of Hydrocarbon Fuel Pyrolysis and Oxidation via a Rate-Based Algorithm.

In this study, we present an automated approach of rate-based skeleton network generation for ReaxFF MD simulation (RxMD-SN) for deriving the reaction kinetic mechanism of large hydrocarbon fuels in pyrolysis and oxidation from large-scale ReaxFF MD simulations. The approach contains the statistical calculation of reaction rate constants and the generation of skeleton reaction networks using a rate-based algorithm. The RxMD-SN method takes advantage of reaction flux ranking at a small time interval in terms of temporal reaction rate to extract the core reaction networks, which allows for keeping the rare reaction events that may be dominant in a certain period of the reaction network. The kinetic models derived from ReaxFF MD simulation in CH4 oxidation can reproduce what was obtained in the ReaxFF MD simulation, which demonstrates the capability of RxMD-SN in capturing the global reaction kinetics. An evaluation of reaction rate constants indicates that close kinetic parameters are shared for n-octane oxidation of similar reaction classes, shared oxidation reactions of CH4 against n-heptane, and shared pyrolysis reactions of the RP-3 surrogate fuel against n-heptane. This capability of RxMD-SN is particularly beneficial in meeting the challenges in characterizing the oxidation reaction kinetics of large hydrocarbon molecules. RxMD-SN approach is potentially a general approach in chemical kinetics modeling on the basis of ReaxFF MD simulations.

Determination of Capsaicinoids in Air Using Colorimetric Detectors

The significant physiological effect of capsaicinoids on the human body is utilized in the fields of food industry, medicine, and internal state security (riot control agents, RCAs). Detection and determination of capsaicinoids in solutions and extracts are fairly well developed, but only marginal attention is given to their detection in the form of aerosols and vapors, which are the primary form of their use as RCAs. In the article, three variants of a simple tube detector for direct detection of capsaicinoids in air (using pelargonic acid vanillylamide – PAVA, as the standard) are presented, utilizing classical color reactions with Turnbull’s blue, Gibbs reagent, and Marquis reagent. The use of these reactions for these purposes is innovative. Each reaction has been optimized and the proposed detectors have been compared, emphasizing their sensitivity, selectivity, and stability. PAVA in the air at a concentration of 0.1 mg/m3 can be detected with the naked eye. The stability of the proposed detectors allows for their commercial use.

Pilot Evaluation of S-(3-[18F]Fluoropropyl)-d-Homocysteine and O-(2-[18F]Fluoroethyl)-d-Tyrosine as Bacteria-Specific Radiotracers for PET Imaging of Infection

PurposeThere is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled d-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of d-tyrosine and d-methionine, O-(2-[18F]fluoroethyl)-d-tyrosine (d-[18F]FET) and S-(3-[18F]fluoropropyl)-d-homocysteine (d-[18F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.Proceduresd-[18F]FET and d-[18F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of d-[18F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [18F]FDG.ResultsIn vitro uptake of both d-[18F]FET and d-[18F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for d-[18F]FPHCys than d-[18F]FET. Blocking experiments with non-radioactive d-[19F]FPHCys confirmed specificity of uptake. In vivo, d-[18F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [18F]FDG showed no significant difference in uptake between infection and inflammation.Conclusionsd-[18F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled d-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.

Discovery of Loureirin analogues with colorectal cancer suppressive activity via regulating cell cycle and Fas death receptor

Chalcones and dihydrochalcones (DHCs) are important bioactive natural products (BNPs) isolated from traditional Chinese medicine. In this study, 13 chalcones were designed with the inspiration of Loureirin, a DHC extracted from Resina Draconis, and synthesized by classical Claisen-Schmidt reactions. Afterwards the reduction reactions were carried out to obtain the corresponding DHCs. Cytotoxicity assay indicated chalcones and DHCs possessed selective cytotoxicity against colorectal cancer (CRC) cells. The preliminary structure-activity relationships (SAR) of these compounds suggested the α, β-unsaturated ketone of the chalcones were crucial for the anticancer activity. Interestingly, compounds 3d and 4c exhibited selective anticancer activity against CRC cell line HCT116 with IC50s of 8.4 and 17.9 μM but not normal cell. Moreover, 4c could also inhibit the migration and invasion of CRC cells. Mechanism investigations showed 4c could induce cell cycle G2/M arrest by regulating cell cycle-associated proteins and could also up-regulate Fas cell surface death receptor. The virtual docking further pointed out that compounds 3d and 4c could nicely bind to the Fas/FADD death domain complex (ID: 3EZQ). Furthermore, silencing of Fas significantly enhanced the proliferation of CRC cells and attenuated the cytotoxicity induced by 4c. These results suggested 4c exerted its anticancer activity possibly regulating cell cycle and Fas death receptor. In summary, this study investigated the anticancer activity and mechanism of Loureirin analogues in CRC, suggesting these compounds may warrant further investigation as promising anticancer drug candidates for the treatment of CRC.

General Regio- and Diastereoselective Allylic C-H Oxygenation of Internal Alkenes.

Branched allylic esters and carboxylates are fundamental motifs prevalent in natural products and drug molecules. The direct allylic C-H oxygenation of internal alkenes represents one of the most straightforward approaches, bypassing the requirement for an allylic leaving group as in the classical Tsuji-Trost reaction. However, current methods suffer from limited scope─often accompanied by selectivity issues─thus hampering further development. Herein we report a photocatalytic platform as a general solution to these problems, enabling the coupling of diverse internal alkenes with carboxylic acids, alcohols, and other O-nucleophiles, typically in a highly regio- and diastereoselective manner.

Beyond the Zincke reaction: Modern advancements in the synthesis and applications of N-aryl pyridinium salts

In this review, we highlight recent advances in the synthesis of N-aryl pyridinium salts, which have moved beyond the classical Zincke SNAr reaction to focus on strategies reliant on C–N bond formation using an ever expanding array of reaction manifolds. This expansion to include C–N bond forming approaches, as well as enabling an unprecedented breadth of both arene and N-heterocyclic coupling partners, has led to a shift in perception of N-aryl pyrdinium salts to now serving as a platform for aryl amine synthesis. As a result, new synthetic applications of these salts have begun to emerge, both utilizing classic (nucleophilic additions, radical reactions, cycloadditions, etc) and emergent transformations such as deaminative transformations, isotopic labeling, and molecular editing. This review provides a timely synopsis of novel N-aryl pyridinium salt syntheses from the last 10 years (2013 to present). These strategies are separated into the two main classes, radical cation and non-radical cation methods. Highlights of recent transformations and applications of the resultant N-aryl pyridinium salts are also discussed to demonstrate the untapped synthetic potential of these scaffolds and highlight areas of continued interest.

Exploring the first-stage ignition and model optimization in the comprehensive study of n-dodecane oxidation

n-Dodecane is commonly employed as a surrogate for investigating the combustion characteristics of jet and diesel fuels. Enhancing comprehension of its combustion behavior and developing accurate chemical kinetics models for simulating combustion is of paramount importance in engine development. This study focuses on a detailed exploration of n-dodecane oxidation kinetics under low-temperature conditions and presents a novel dataset concerning the first-stage ignition delay time. A broad spectrum of experimental conditions is investigated, encompassing a range of temperature (600 ∼ 1350 K), pressure (5 ∼ 20 atm), equivalence ratios (0.5 ∼ 1.0), and dilution gases (N2 and Ar). Additionally, combustion experiments in a pure oxygen environment are performed, contributing valuable data to existing research. To enhance the precision of the chemical reaction kinetics model of n-dodecane, this study integrates updated rate coefficients obtained from the latest theoretical calculations for specific reaction classes. The improved rate rule provides a more accurate reference for the construction of the chemical reaction kinetics model of long straight alkane. The resulting improved model excels in accurately predicting both the first-stage ignition delay time and the total ignition delay time under a wide range of operational conditions. Additionally, the model performance is rigorously evaluated through a comprehensive assessment against a diverse array of datasets gathered from various literature references. The results show that, in contrast to the previously proposed model, this enhanced model provides highly reliable predictions over a broad range of parameters.

Frontal Polymerization for the Rapid Obtainment of Polymer Composites.

Among the different polymerization techniques, frontal polymerization (FP) has gained high interest from the scientific community because of its peculiar characteristics: in particular, compared to classic polymerization reactions, FP allows for a better exploitation of the heat of polymerization involved, without requiring any external energy input apart from an initial photo or thermal ignition that triggers the reaction. The latter usually propagates in a few tenths of seconds or (at most) minutes through a hot self-sustaining polymerization front, giving rise to the formation of fully cured thermosetting networks or thermoplastic polymers. Furthermore, different polymerization mechanisms can be involved in FP reactions, comprising cationic or anionic, ring-opening metathesis, and free-radical polymerization, among others. Further, it is possible to run FP reactions in bulk, in solution, or even using solid monomers if they are melted at the temperature of the front, notwithstanding the possibility of using reactive systems containing fillers or fiber/fabric reinforcements. In this context, the use of FP is becoming very important also for the design and production of advanced (nano)composite materials, saving processing time and achieving the completeness of the curing reaction, even in the presence of high filler/reinforcement loadings. Therefore, this mini-review aims to provide the reader with the basics of FP and its main peculiarities, even in the context of preparing high-performing composites. In this respect, some recent case studies witnessing the potentialities of frontal polymerization for the design of advanced (nano)composite systems will be elucidated. Finally, some perspectives about possible future developments will be proposed.

Emergence of non-trivial solutions from trivial solutions in reaction–diffusion equations for pattern formation

Reaction–diffusion equations serve as fundamental tools in describing pattern formation in biology. In these models, nonuniform steady states often represent stationary spatial patterns. Notably, these steady states are not unique, and unveiling them mathematically presents challenges. In this paper, we introduce a framework based on bifurcation theory to address pattern formation problems, specifically examining whether nonuniform steady states can bifurcate from trivial ones. Furthermore, we employ linear stability analysis to investigate the stability of the trivial steady-state solutions. We apply the method to two classic reaction–diffusion models: the Schnakenberg model and the Gray–Scott model. For both models, our approach effectively reveals many nonuniform steady states and assesses the stability of the trivial solution. Numerical computations are also presented to validate the solution structures for these models.

Highly pathogenic avian influenza H5N8 and H5N1 outbreaks in Algerian avian livestock production

Avian Alpha-influenza-virus (AIV) massively affects poultry, targeting mainly the respiratory tract for virus replication. Recently, two major H5N8 and H5N1 outbreaks caused tremendous losses in Algerian poultry. The clinical symptoms that had not been seen in the past didn’t prompt a rapid reaction to control the epidemics. We report here the characteristics of these outbreaks and the epidemiological status of AIV in Algeria. Following autopsy observation samples from target organs were taken and analyzed by the classical real-time reverse transcription polymerase chain reaction (RRT-PCR). Specific PCR HA and NA identification was used for subtyping H5 and N1/N8 genes. Systemic damage was observed in the upper-respiratory tracts with hemorrhagic and congestive tracheas, lungs, proventriculus, gut, and cecal tonsils were bloody. Out of 77 positive cases 13 were H5N8, 8 H5N1, and 10 H5Nx strains. These findings raise questions about the strain’s pathotype considering severe organ damage and high mortality.

Iron‐Catalyzed C−C and C−N Bond‐Forming Tandem Amidation Offering Access to 3‐Amino‐3‐Aminomethyl‐2‐Oxindole Frameworks

AbstractAn iron‐catalyzed protocol for the synthesis of 3‐amino‐3‐aminomethyl‐2‐oxindole heterocyclic structures is disclosed employing isatins and non‐nucleophilic N‐methoxybenzamides. This reaction class is associated with broad scope and tolerates numerous functionalities, such as fluoro, chloro, bromo, iodo, trifluoromethyl, nitrile, ester, ether, and alkenyl, including heteroaryl – thiophene, benzothiophene, carbazolyl, indolyl, eugenol, and polycyclic cholesterol moieties. Detailed mechanistic investigations reveal that the reaction proceeds via iron‐catalyzed N−O bond cleavage in N‐methoxybenzamides, generating formaldehyde and benzamide, and through the intermediacy of isatin‐ketimines and N‐(hydroxymethyl)benzamides. Overall, this amidation reaction involves one C−C and two C−N bond‐forming tandem processes, providing a range of β‐amino‐aminomethyl‐oxindoles (45 examples) in up to 88% yields.

Selective Hydrosilylation and Hydroboration of Allenes Catalyzed by Cobalt‐Pincer Complexes

AbstractAchieving precise control over regioselectivity and stereoselectivity in the hydroelementation of terminal allenes presents a formidable challenge. Despite the existence of various catalytic methods for their functionalization, this entire class of reactions remains significantly underdeveloped and demands extensive research. Here, we report a method for the hydroelementation of allenes using inexpensive PN5P pincer cobalt complexes built on a triazine backbone. Depending on the substituent at the ring, the method enables the selective synthesis of E‐alkenylsilane or Z‐allylborane derivatives. In the presented approach, silanes and pinacoloboranes play a dualistic role of simultaneous activator and substrate excluding the need for the addition of external bases. Finally, the application potential of the obtained compounds was demonstrated by performing further functionalizations of the obtained compounds.

Click Chemistry: Reaction Rates and Their Suitability for Biomedical Applications.

Click chemistry has become a commonly used synthetic method due to the simplicity, efficiency, and high selectivity of this class of chemical reactions. Since their initial discovery, further click chemistry methods have been identified and added to the toolbox of click chemistry reactions for biomedical applications. However, selecting the most suitable reaction for a specific application is often challenging, as multiple factors must be considered, including selectivity, reactivity, biocompatibility, and stability. Thus, this review provides an overview of the benefits and limitations of well-established click chemistry reactions with a particular focus on the importance of considering reaction rates, an often overlooked criterion with little available guidance. The importance of understanding each click chemistry reaction beyond simply the reaction speed is discussed comprehensively with reference to recent biomedical research which utilized click chemistry. This review aims to provide a practical resource for researchers to guide the selection of click chemistry classes for different biomedical applications.

Toehold Strand Displacement-Mediated Exponential HCR for Highly Sensitive and Specific Analysis of miRNA in Living Cells.

As an important disease biomarker, the development of sensitive detection strategies for miRNA, especially intracellular miRNA imaging strategies, is helpful for early diagnosis of diseases, pathological research, and drug development. Hybridization chain reaction (HCR) is widely used for miRNA imaging analysis because of its high specificity and lack of biological enzymes. However, the classic HCR reaction exhibits linear amplification with low efficiency, limiting its use for the rapid analysis of trace miRNA in living cells. To address this problem, we proposed a toehold-mediated exponential HCR (TEHCR) to achieve highly sensitive and efficient imaging of miRNA in living cells using β-FeOOH nanoparticles as transfection vectors. The detection limit of TEHCR was as low as 92.7 fM, which was 8.8 × 103 times lower compared to traditional HCR, and it can effectively distinguish single-base mismatch with high specificity. The TEHCR can also effectively distinguish the different expression levels of miRNA in cancer cells and normal cells. Furthermore, TEHCR can be used to construct OR logic gates for dual miRNA analysis without the need for additional probes, demonstrating high flexibility. This method is expected to play an important role in clinical miRNA-related disease diagnosis and drug development as well as to promote the development of logic gates.

Facile access to benzofuran-based bis-stilbene for organic laser dyes

A concise and efficient synthetic protocol for the synthesis of furan-based bis-stilbene derivatives (BPBFCz1) was described, which is a very promising organic laser dye. Starting with 4,4’-diethynylbiphenyl, BPBFCz1 was prepared with a total yield of 40% through a three-step classical reaction of Sonogashira Coupling, intramolecular cyclization of 2-alkynyl phenol, and Buchwald Hartwig cross-coupling. The crystal structure of BPBFCz1 was presented for the first time. The synthesis strategy was applied to the synthesis of other three materials with similar structure and the yields of 28.6–36.6% were obtained.

Discrimination of chiral amino acid enantiomers through photoelectrochemical sensing platform

Chirality plays fundamental functions in the activity of biological molecules and broad classes of chemical reactions, but its recognition and detection still remain a great challenge. Herein, inspired by the stereo-control characteristics of chiral amino acids adjacent to the active sites of natural enzymes, a photoelectrochemical (PEC) chiral sensor was constructed by encapsulating Au nanoparticles with the recognition unit l-Cysteine into mesoporous BiVO4 skeleton. The chiral sensor exhibits a high sensitivity and selectivity discrimination of 3,4-dihydroxyphenylalanine (DOPA) enantiomers. The possible mechanism of enantioselectivity was proposed with the guidance of DFT calculations, suggesting that the origin of chiral selectivity lies in the different hydrogen bonds forms between l-Cys and DOPA. This work provides a powerful strategy for constructing PEC chiral sensing device with excellent chiral recognition performance.