Ring-opening Mechanism Research Articles

A Novel Rhodamine B Fluorescent Probe Derived from Carboxymethyl Chitosan for the Selective Detection of Fe3.

In this study, we synthesized a fluorescent material by modifying the C-2 amino group of carboxymethyl chitosan with a rhodamine B derivative, which was proposed and demonstrated using 1H NMR and FT-IR measurements. A series of experiments including selectivity, sensitivity, reversibility, pH, and water content were conducted to investigate the fluorometric and colorimetric properties of the grafted polymer. Utilizing a Fe3+-induced ring-opening mechanism of the rhodamine B spirolactam, we found that the grafted polymer exhibited a highly selective fluorescence response to Fe3+, with enhanced fluorescence at 583 nm compared to other tested metal ions and anions, accompanied by the characteristic absorption peak of rhodamine B that appeared at 561 nm with a noticeable color change from colorless to pink, facilitating visual observation. Additionally, the modified probe, composed of carboxymethyl chitosan, was easily regenerated through treatment with EDTA.

Origin of a Kinetically Selective Route for Thermoreversible Valence Tautomerism-Based Photoswitching in O-Heterocycles Containing Conjugated Dienes.

The thermal electrocyclic ring opening of fused cis-cyclobutene to cis,cis-diene is prohibited according to the Woodward-Hoffmann (WH) rules; nonetheless, experiments provide firm evidence for their formation. However, the mechanism, electronic structure, and behavior during the reaction are ambiguous. Herein, we attempt to gain insights into the mechanism of thermal ring opening in four O-heterocycles containing a conjugated diene as the core skeleton. The results emphasize that the reaction initiates with a conrotatory ring opening to produce a cis,trans-diene as a strained transient intermediate following the WH rules but ultimately leads to a forbidden product. The conversion of cis,trans-diene to cis,cis-diene is kinetically preferred through double-bond rotation, involving the formation of a singlet biradicaloid. The expected H-shift is unfavorable because the requirement of suprafacial H transfer incorporates additional strain, while the transfer of other available H is symmetry-forbidden. The increased electrophilicity at O promotes C-O dissociation in the 8-membered cyclic cis,trans-dienes with fused benzene. This enables thermoreversible photoswitching via a two-step mechanism and kinetically refutes the direct disrotatory pathway. These systems can outperform energy storage, and critical insight into their mechanism with the aid of comprehensive electronic structure analysis would assist in their rational design in the future.

Zinc-Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes.

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94 % and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

Acid-base neutralization strategy for immobilization amino acid ionic liquid within sulfonic acid-based COF as a switch for selective conversion of epoxides

Covalent organic frameworks (COFs) and ionic liquids (ILs) as raw materials exhibit effective catalytic performance and adsorption capabilities in the reaction of epoxides and atmospheric CO2, respectively. Nonetheless, bonding modes between ILs and COFs have restricted their utility, thereby constraining the in-depth study of synergistic catalytic mechanisms over these composite catalysts. Herein, a heterogeneous composite ([DBUH]2Cys@COF-X) were successfully prepared by the facile acid-base neutralization method, incorporating varying amounts of amino acid ILs ([DBUH]2Cys) into the pore channels of sulfonic acid-based COF (TpPa-SO3H). [DBUH]2Cys@COF-3 efficiently catalyzed epichlorohydrin with a yield of 96.38 % without any solvent or co-catalyst under atmospheric CO2. Notably, larger sterically hindered epoxides were selectively blocked on the surface of [DBUH]2Cys@COF-3, enabling [DBUH]2Cys@COF-3 to act as a gatekeeper for selectively catalyzing small sterically hindered epoxides due to [DBUH]2Cys was distributed within the pore channels of [DBUH]2Cys@COF-3. Through DFT calculations, comprehensive understanding of the synergistic activation conferred of -COO- and [DBUH]+ towards CO2 and epoxides in [DBUH]2Cys@COF-3 and the ring-opening mechanism was clarified. This work presents a fresh outlook on the catalyst design by the facile acid-base neutralization method for efficiently catalyzing small-hindered epoxides under atmospheric CO2.

Switching between the [2π+2σ] and Hetero-[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles.

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S-BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid-catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3-benzylideneindoline-2-thione derivatives have been established. The first hetero-(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3-catalyzed [2π+2σ] reaction with 1,1,2-trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E-1,1,2-trisubstituted alkenes. Additionally, the hetero-(4+3) cycloaddition may involve a concerted nucleophilic ring-opening mechanism.

Ring–Opening Mechanism of O‐heterocycles into α,ω‐Diols over Ni−La(OH)3: C−O Bond Hydrogenolysis of THFA to 1,5‐Pentanediol as a Case Study

AbstractThe elucidation of the ring–opening reaction mechanism is a critical step towards improving the catalytic performance for the conversion of biomass into value–added chemicals. Herein, we focused on the stepwise C−O bond hydrogenolysis mechanism of oxygen–containing heterocycles (O‐heterocycles) into α,ω‐diols, in particular THFA to 1,5‐PeD, over selective Ni−La(OH)3 in hydrogen–donor isopropanol. A mechanistic study was carried out on a structurally well–defined Ni−La(OH)3, where the mechanism was elucidated using a combination of kinetic and 13C NMR isotope labeling experiments. It was suggested that both Ni nanoparticles and La(OH)3 support play a critical role in the reaction mechanism, where basic hydroxide species of the support initially deprotonate the CH2OH and −OH modified furan, tetrahydrofuran and tetrahydropyran rings, adsorbing them chemically on the catalyst surface. This step is followed by a direct hydride attack on the second carbon atom of these rings, which is proposed to be the key step for ring cleavage, as indicated by the increased deuteration at this position. In addition to the direct hydrogenolysis using gaseous H2, it is assumed that a catalytic transfer hydrogenolysis reaction (CTH) reaction of THFA is proposed to proceed via the dehydrogenation of isopropanol over isolated Ni species, forming hydrogen species that can be adsorbed on the Ni surface or desorb as H2 molecules.

Elucidation of the Pyridine Ring-Opening Mechanism of 2,2'-Bipyridine or 1,10-Phenanthroline Ligands at Re(I) Carbonyl Complexes.

The cleavage of the C-N bonds of aromatic heterocycles, such as pyridines or quinolines, is a crucial step in the hydrodenitrogenation (HDN) industrial processes of fuels in order to minimize the emission of nitrogen oxides into the atmosphere. Due to the harsh conditions under which these reactions take place (high temperature and H2 pressure), the mechanism by which they occur is only partially understood, and any study at the molecular level that reveals new mechanistic possibilities in this area is of great interest. Herein, we unravel the pyridine ring-opening mechanism of 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) ligands coordinated to the cis-{Re(CO)2(N-RIm)(PMe3)} (N-RIm= N-alkylimidazole) fragment under mild conditions. Computational calculations show that deprotonation of the pyridine ring, once dearomatized, is crucial to induce ring contraction, triggering extrusion of the nitrogen atom from the ring and cleavage of the C-N bond. It is noteworthy that different products (regioisomers) are obtained depending on whether the ligand used is bipy or phen due to the additional rigidity and stability conferred by the central ring of the phen ligand, an issue also addressed and clarified computationally. Strong support for the proposed mechanism is provided by the characterization and isolation, including three single-crystal X-ray diffraction structures, of several of the proposed reaction intermediates.

Analysis of failure and optimization study of stoppage ring opening mechanism in sleeve valve casing material

In the context of deep-buried sleeve valve construction, two significant challenges in grouting operations involve the material infusion and subsequent failure of the casing material's opening loop. This study combines indoor experiments and field studies to investigate the optimization strategies for sleeve valve construction by introducing aggregate additives. The research begins with a theoretical analysis of the weak formation of the stoppage ring, scrutinizing its failure causes under deep-buried conditions. It further delves into mechanism study on optimizing the opening loop mechanism of the stoppage ring post the addition of crushed stone aggregates. Simultaneously, indoor experiments focus on assessing the fracture characteristics of aggregate-casing materials. These findings are then applied to on-site grouting loop tests. The experiments demonstrate that the inclusion of aggregates not only enhances the intact opening probability and operational efficiency of casing materials but also disperses the impact of casing material aggregates within the stratum. This dispersion significantly reinforces the crushed stone-mud slurry framework within the stratum, ultimately contributing to improved stratum uniformity and stability. Through a comprehensive investigation into the casing material's opening loop mechanism, a clearer understanding of the causes of opening failure is achieved, leading to proposed optimization methodologies. These findings aim to provide both theoretical support and practical guidance for improving designs and optimizing fluid systems in diverse engineering contexts.

Sustainable approach for catalytic epoxidation of oleic acid followed byin situring-opening hydrolysis with applied ion exchange resin

AbstractVegetable oils are rich in unsaturated bonds that can be converted to epoxidized oleic acid. They are considered sustainable, renewable, and also environmentally friendly. To date, there is a paucity of studies on production of dihydroxystearic acid (DHSA) using an eco-friendly ion exchange resin as it is not fully utilised. As a result, the aim of this study is to elucidate the mechanism of ring-opening by hydrolysis for the production of DHSA using amberlite IR-120H as a catalyst. The process of epoxidizing oleic acid involved thein situgeneration of performic acid, which was then used to convert oleic acid into epoxidized oleic acid. This performic acid was created by combining formic acid, serving as the oxygen carrier, with hydrogen peroxide, acting as the oxygen donor. Under optimal conditions, the maximum relative conversion of oleic acid to oxirane was attained, with up to 85 %. Overall, DHSA with a high hydroxyl value (182 mg KOH/g), was successfully produced from oleic acid usingin situhydrolysis of epoxidized oleic acid.

Insight into catalytic contribution of non-halogen cation and anion for CO2 conversion into cyclic carbonate

Non-halogen ionic liquids are considered efficient catalyst for CO2 conversion into cyclic carbonates. In this work, six carboxylic acid ionic liquids with different types and sizes of cations are designed and synthesized to systematically investigate the catalytic contribution of the non-halogen cation and anion for CO2 conversion into cyclic carbonate. The result shows that the anion could improve the catalytic activity by improve the basicity of ionic liquids, and the cation that has a weak interaction with anion is more conducive for the reactivity. Further, the reaction mechanism is deeply studied by using the optimized [P4444][IsoNic]: two reaction intermediates are captured by In-situ infrared, combined with DFT calculation, the anion directly inducing ring-opening mechanism is proposed. This work provides an in-depth understanding of catalytic contribution of non-halogen ionic liquids used in cycloaddition reaction.

Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.

Catalytic gasification of anthracene in supercritical water with Ni/TiO2 catalyst: Products distribution and kinetics

Supercritical water gasification (SCWG) is a clean and efficient utilization way of coal to produce hydrogen-rich gas. As the consumption of PAHs is the rate-determining step to the rapid gasification of coal in SCW, anthracene was used as the simplest model of PAHs to investigate the ring-opening and gasification mechanism of PAH compounds in supercritical water (SCW). The SCWG experiments of 7.5 wt% anthracene were carried out in SCW under various temperatures (400–550 °C) and residence times (5–30 min). Ni/TiO2 catalysts were added to achieve the fast and complete gasification of anthracene, and a carbon gasification efficiency of 95.73% was achieved at 500 °C, which was 100 times higher than 0.95% of the non-catalytic condition. A kinetic model including a detailed reaction pathway for anthracene was successfully proposed to reveal the catalytic mechanism of anthracene gasification in SCW. The results indicated that the addition of Ni/TiO2 effectively reduced the activation energy of anthracene hydrogenation to generate CH4, and this reaction was most critical for the generation of CH4. This work guided the determination of key parameters for industrial-scale reactors to achieve an optimal design, providing a promising method for in-situ elimination of char during SCWG of coal.

What is the Mechanism of H3+ Formation from Cyclopropane?

We examine the possibility that three hydrogen atoms in one plane of the cyclopropane dication come together in a concerted "ring-closing" mechanism to form H3+, a crucial cation in interstellar gas-phase chemistry. Ultrafast strong-field ionization followed by disruptive probing measurements indicates that the formation time of H3+ is 249 ± 16 fs. This time scale is not consistent with a concerted mechanism, but rather a process that is preceded by ring opening. Measurements on propene, an isomer of cyclopropane, reveal the H3+ formation time to be 225 ± 13 fs, a time scale similar to the H3+ formation time in cyclopropane. Ab initio molecular dynamics simulations and the fact that both dications share a common potential energy surface support the ring-opening mechanism. The reaction mechanism following double ionization of cyclopropane involves ring opening, then H-migration, and roaming of a neutral H2 molecule, which then abstracts a proton to form H3+. These results further our understanding of complex interstellar chemical reactions and gas-phase reaction dynamics relevant to electron ionization mass spectrometry.

Cost-effective fixation of CO2 into cyclic carbonates catalyzed by Zn bromide-based deep eutectic ionic liquid

In this work, we designed a novel thermally stable Zn bromide-based deep eutectic ionic liquid (DEIL), synthesized from tetralkylphosphonium bromide (Bu4PBr) and ZnBr2 by a facile heating method. The structural changes and the physical properties of the catalyst were in-depth investigated. Among all the DEILs, ZnBr2·2Bu4PBr showed high activity, achieved 98.2% propylene carbonate (PC) yield at a low catalyst usage (0.15 mol%), and remained good stabilities for 8 cycles. Furthermore, based on experimental results and DFT calculations, we found that Bu4P+ cation of DEIL served as a frame charge-balanced species interacting with three possible anions of ZnBr42−, ZnBr3− and Br−. The interaction is accompanied by a reversible pre-equilibrium in which [Bu4P]2[ZnBr4] could dissociate and produce the true catalytically active species, [Bu4P][ZnBr3] and Bu4PBr. Meanwhile, a possible ring-opening mechanism was proposed, in which the synergetic effect of cations and anions in the catalytic system can promote ring-opening. The significance of this study is that it provides guidance for developing metal bromide-based DEILs for carbonate synthesis.

Nucleophilic epoxide ring opening in the system "epichlorohydrin–carboxylic acids–tetrabutylammonium iodide–solvent (e=15.1–28.7)"

The mechanism of the oxirane ring opening by carboxylic acids with different volume of substituents in the system "epichlorohydrin(ЕCH)–RCOOH–tetrabutylammonium iodide–solvent (=15.1–28.7)" was studied in the excess of ECH at the temperatures of 40–800C by methods of chemical kinetics and correlation analysis. The effects of solvent polarity (ECH and its mixtures with THF and nitrobenzene), temperature, and spatial structure (topological steric effect index TSEI) of carboxylic acids on the proceeding of the reaction were investigated. The structure of the reaction products was determined by gas chromatography–mass and 1H NMR spectroscopy. It was found that the reaction accelerates with a decrease in the solvent polarity, an increase in temperature and steric effect in the structure of the reagent. It was shown that the tetraalkylammonium carboxylate (R'4N+–OOCR) which formed in situ causes the final product formation in the rate-determining step of the reaction mechanism.

Ring-Opening Cyclization (ROC) of Aziridines with Propargyl Alcohols: Synthesis of 3,4-Dihydro-2H-1,4-oxazines.

Activated aziridines react with propargyl alcohols in the presence of Zn(OTf)2 as the Lewis acid catalyst following an SN2-type ring-opening mechanism to furnish the corresponding amino ether derivatives. Those amino ethers further undergo intramolecular hydroamination via 6-exo-dig cyclization in the presence of Zn(OTf)2 as the catalyst and tetrabutylammonium triflate salt as an additive under one-pot two-step reaction conditions. However, for nonracemic examples, ring-opening and cyclization steps were conducted under two-pot conditions. The reaction works well without any additional solvents. The final 3,4-dihydro-2H-1,4-oxazine products were obtained with 13 to 84% yield and 78 to 98% enantiomeric excess (for nonracemic examples).

PH-Triggered Charge Reversible Fluorescent Probe for Simultaneous Imaging of Lipid Droplets and Nucleoli in Living Cells.

Cooperation between organelles is essential to maintain the normal functions of cells. Lipid droplets (LDs) and nucleoli, as important organelles, play an important role in the normal activities of cells. However, due to the lack of appropriate tools, in situ observation of the interaction between them has been rarely reported. In this work, taking into full consideration the pH and charge differences between LDs and nucleoli, a pH-triggered charge reversible fluorescent probe (LD-Nu) was constructed based on a cyclization-ring-opening mechanism. The in vitro pH titration experiment and 1H NMR showed that LD-Nu gradually transferred from the charged form to the electroneutral form with the increase of pH, and thus, the conjugate plane was reduced and its fluorescence blue-shifted. Most importantly, the physical contact between LDs and nucleoli was visualized for the first time. Meanwhile, the relationship between LDs and nucleoli was also further investigated, and the results showed that their interaction was more liable to be affected by the abnormality of LDs than those of nucleoli. Moreover, the cell imaging results displayed that the LDs both in the cytoplasm and nucleus were observed using the probe LD-Nu, and interestingly, the LDs in the cytoplasm were more susceptible to external stimuli than those in the nucleus. In a word, the probe LD-Nu can serve as a powerful tool for further exploration of the interaction mechanism between LDs and nucleoli in living cells.

Phosphaphenanthrene-Functionalized Benzoxazines Bearing Intramolecularly Hydrogen-Bonded Phenolic Hydroxyl: Synthesis, Structural Characterization, Polymerization Mechanism, and Property Investigation

Hydrogen bonding in thermosetting resins can have a significant influence on the polymerization processes and the properties of corresponding thermosets, but its role in the polymerization of benzoxazine resins remains unclear. Here, we synthesized two novel phosphaphenanthrene-functionalized benzoxazine monomers from 2-6-oxido-6H-dibenz-[c,e][1,2]oxaphosphorin-1,4-dihydroxy phenylene, aniline/furfurylamine, and paraformaldehyde and investigated the structures by 1H, 13C, and 31P NMR, Fourier transform infrared (FT-IR), elemental analysis, and high-resolution mass spectrometry. Ring-opening polymerizations of both monomers were then studied by differential scanning calorimetry (DSC) and in situ FT-IR spectroscopy, and the resulting thermosets exhibited high thermal stability and low flammability. Density functional theory (DFT) calculations suggested that intramolecular hydrogen bonds are preferably formed between the phenolic −OH and the P═O in the phosphaphenanthrene functionality for both monomers, which is in line with the experimental results. We proposed a cation-activated ring-opening polymerization mechanism where intramolecular hydrogen bonding plays a pivotal role. The combination of experimental and computational effort provides molecular-level insights into intramolecular hydrogen bonding and its role in polymerization mechanisms in benzoxazine chemistry as well as a new angle for the design of high-performance thermoset polymers.

Discovery, synthesis and mechanism study of 2,3,5-substituted [1,2,4]-thiadiazoles as covalent inhibitors targeting 3C-Like protease of SARS-CoV-2

The 3C-like protease (3CLpro) is essential for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making it a promising target for the treatment of corona virus disease 2019 (COVID-19). In this study, a series of 2,3,5-substituted [1,2,4]-thiadiazole analogs were discovered to be able to inhibit 3CLpro as non-peptidomimetic covalent binders at submicromolar levels, with IC50 values ranging from 0.118 to 0.582 μM. Interestingly, these compounds were also shown to inhibit PLpro with the same level of IC50 values, but had negligible effect on proteases such as chymotrypsin, cathepsin B, and cathepsin L. Subsequently, the antiviral abilities of these compounds were evaluated in cell-based assays, and compound 6g showed potent antiviral activity with an EC50 value of 7.249 μM. It was proposed that these compounds covalently bind to the catalytic cysteine 145 via a ring-opening metathesis reaction mechanism. To understand this covalent-binding reaction, we chose compound 6a, one of the identified hit compounds, as a representative to investigate the reaction mechanism in detail by combing several computational predictions and experimental validation. The process of ring-opening metathesis was theoretically studied using quantum chemistry calculations according to the transition state theory. Our study revealed that the 2,3,5-substituted [1,2,4]-thiadiazole group could covalently modify the catalytic cysteine in the binding pocket of 3CLpro as a potential warhead. Moreover, 6a was a known GPCR modulator, and our study is also a successful computational method-based drug-repurposing study.

Ring-opening mechanism of epoxides with alcohol and tertiary amines

The ring-opening reaction of epoxides with alcohol and tertiary amines was studied. NMR spectroscopy analysis confirmed that glycidol has a different ring-opening polymerization mechanism than other epoxides in the presence of tertiary amines.