Search Results (424)

Core–corona polymer microsphere-immobilized MacMillan catalysts were synthesized via ionic immobilization of a MacMillan catalyst precursor onto core–corona polymer microspheres bearing sulfonic acid moieties in their side chains. The resulting heterogeneous catalysts were applied to the asymmetric Diels–Alder reaction between trans-cinnamaldehyde and 1,3-cyclopentadiene under continuous-flow conditions. The effects of solvent, flow rate, substrate concentration, core particle size, and corona chain length on catalytic performance were systematically investigated. High enantioselectivities of 92% ee for the exo isomer and 95% ee for the endo isomer were achieved using the catalyst with the optimized structure under optimized conditions. Furthermore, the durability and substrate scope of the catalyst were evaluated in continuous-flow reactions, demonstrating its high stability and practical applicability. Full article

The development of bio-based plasticizers is increasingly important due to regulatory restrictions on several phthalates, growing concerns over plasticizer migration and toxicity, and the demand for renewable materials. In this work, eleven novel furfural-derived bio-based plasticizers were synthesized and evaluated in polylactic acid (PLA) at 15 wt% loading via melt compounding. Their influence on the thermomechanical properties of PLA was investigated, enabling the establishment of structure–property relationships. Hansen Solubility Parameters (HSPs) were used to predict plasticizer–PLA compatibility and correlate theoretical predictions with experimental performance. All developed bio-plasticizers exhibited onset degradation temperatures exceeding 225 °C, ensuring suitability for melt processing with PLA. Increasing the alkyl chain length in the diester bio-plasticizers reduced plasticization efficiency, consistent with lower predicted compatibility based on HSP analysis. The most promising candidates, namely 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2,3-dihexyl ester (F/MA-C6), 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2,3-dioctyl ester (F/MA-C8), and 1,1′-[oxybis(1-methyl-2,1-ethanediyl)]bistetrahydrofuroate (Bis-THF), substantially enhanced polymer chain mobility, reducing the glass transition temperature to approximately 28–35 °C compared to 60 °C for neat PLA. These bio-plasticizers also demonstrated outstanding plasticizing efficiency, achieving elongations at break exceeding 245%, compared with 4.5% for neat PLA. These results demonstrate that furfural-derived plasticizers are promising sustainable alternatives to conventional fossil-based plasticizers for flexible PLA applications. Full article

3,4-dihydrocoumarins and spiro compounds constitute an important class of privileged frameworks present in a wide variety of natural and synthetic molecules with diverse applications. In this study, we developed an organocatalytic methodology for the construction of complex and diverse chiral spiro-bridged 3,4-dihydrocoumarins through a Diels–Alder/Nucleophilic ring-closing cascade via trienamine activation. The reaction proceeds efficiently with different trienamine precursors and a range of coumarin-3-carboxamides, which act as both dienophile and intramolecular nucleophile species. This process affords the desired products in good yields and with a high degree of stereocontrol. Furthermore, several transformations on the newly formed spiro-piperidone ring demonstrate the synthetic utility of the obtained compounds. Full article

Background/Objectives: Antibody selection is critical for advancing pretargeted PET imaging toward clinical translation. This study directly compared two clinically approved anti-HER2 antibodies—trastuzumab and pertuzumab—within an identical pretargeting system, utilizing the specific chemical ligation between tetrazine and trans-cyclooctene (TCO) via the inverse electron-demand Diels–Alder (IEDDA) cycloaddition. Methods: In HER2-positive SKOV3 tumor-bearing mice, TCO-conjugated antibodies were administered 1–13 days prior to injection of a fluorine-18-labeled tetrazine probe ([¹⁸F]PEG₁₂-Tz). Results: Both strategies enabled high-contrast imaging, overcoming the kinetic mismatch between slow-clearing antibodies and the short-lived ¹⁸F isotope. Distinct profiles were observed: pertuzumab-TCO yielded higher tumor uptake and a broader imaging window (3–13 days), whereas trastuzumab-TCO resulted in lower uptake and a narrower window (1–5 days). These differences are not affinity-driven, as both conjugates showed similar Kd values (~11–14 nM). Instead, pertuzumab-TCO’s superiority stems from a dual mechanism: (1) slower cellular internalization (65.1% vs. 94.0% at 60 min) preserves surface TCO for click reaction; and (2) markedly slower blood clearance (t_1/2β = 285.9 h vs. 106.0 h) ensures sustained bioavailability and tumor extravasation. Conclusions: This head-to-head evaluation demonstrates that epitope-dictated internalization and clearance are decisive parameters for antibody selection, providing a mechanism-based framework for optimizing pretargeted imaging. Full article

Thermosets are widely used in engineering applications due to their high mechanical strength, thermal stability, and chemical resistance; however, their permanently crosslinked networks also limit repair, reshaping, and recycling. Dynamic covalent chemistry offers a route to addressing these limitations through the incorporation of reversible bond exchange into thermoset networks. A range of dynamic thermosets has been developed based on transesterification, Diels–Alder reactions, imine exchange, disulfide metathesis, boronic ester exchange, and siloxane equilibration, enabling self-healing, reprocessing, welding, and closed-loop recycling. This review examines representative dynamic thermosets in terms of exchange mechanisms, network topology evolution, and macroscopic response. By correlating molecular exchange processes with network-level mechanics and macroscopic performance, this review identifies design principles for dynamic thermosets with improved sustainability and processing compatibility. Full article

The influence of steric hindrance caused by the dienophiles on the stereoselectivity of cycloadditions of 2H-pyran-2-ones with maleimides was investigated in this study. It was found that sufficiently bulky N-substituents on the maleimides (such as N-triphenylmethyl) can cause the cycloaddition to proceed differently than expected, thus yielding asymmetric exo,endo-bicyclo[2.2.2]octenes instead of the commonly obtained symmetric exo,exo products. Furthermore, the incorporation of an N-triphenylmethyl group, which induces highly diastereoselective formation of asymmetric exo,endo adducts and can later be easily removed under acidic conditions, can be described as an example of an efficient exo,endo-diastereoselective auxiliary. Full article

Dynamic covalent bonds are commonly used to maintain the self-healing properties of polyurethanes and facilitate resource recycling. However, relying on a single type of dynamic covalent bond often makes it difficult to effectively regulate both mechanical and self-healing properties across a wide temperature range. In this study, a self-synthesized chain extender containing disulfide bonds was introduced into a polyurethane system, leading to the development of a novel dual-dynamic covalent bond self-healing polyurethane (SSDA-PU). Innovatively, this SSDA-PU demonstrates self-healing properties across a wide temperature range. The successful synthesis of the chain extender and the incorporation of both disulfide bonds and Diels–Alder (DA) bonds were confirmed using FTIR and Raman spectroscopy. The physical characteristics and self-healing performance were comprehensively evaluated through multi-scale testing and characterization, including thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), hardness testing, mechanical tensile tests, and self-healing experiments. The underlying synergistic self-healing mechanism was subsequently elucidated. Findings showed that a higher R-value (isocyanate index) in SSDA-PU leads to over-crosslinking, while an R-value of 1.7 achieves the best overall mechanical performance, with tensile strength and elongation at break reaching 21.1 MPa and 755.17%, respectively. Additionally, SSDA-PU demonstrated the capacity for multiple healing cycles, with an initial self-healing efficiency of 90.38%, which remained notably high at 59.21% even after three damage-healing cycles. Importantly, SSDA-PU exhibited healing capabilities even at relatively low temperatures. Cracks in SSDA-PU can be effectively repaired through the synergistic action of disulfide bond exchange, hydrogen bond dissociation, and thermally reversible DA reactions. SSDA-PU also shows excellent recyclability, offering valuable insights for the practical engineering application of functional polyurethanes. Full article

The formation of recyclable polyethylene materials is significantly limited by traditional crosslinking methods, which involve solvent-heavy processes and permanent chemical bonds that cannot be undone. Herein, we report an environmentally friendly and scalable approach to construct a thermo-reversible polyethylene network (PE-g-DA) via solvent-free, one-step melt processing based on furan–maleimide Diels–Alder (D–A) dynamic covalent chemistry. Furan-functionalized polyethylene was dynamically crosslinked with bismaleimide during melt mixing, fully compatible with conventional polyolefin processing techniques. FTIR spectroscopy, temperature-dependent solubility, and differential scanning calorimetry collectively confirm the reversible formation and dissociation of D–A adducts, enabling thermal switching of the network structure. Equilibrium swelling experiments based on the Flory–Rehner model indicate that the crosslink density can be precisely controlled by varying the bismaleimide content. As a result, PE-g-DA exhibits significantly enhanced tensile strength while maintaining high ductility at moderate crosslink densities. Notably, the dynamic network allows efficient thermal reprocessing, with recycled samples retaining approximately 93% and 80% of their original tensile strength after the first and second reprocessing cycles, respectively. Moreover, intrinsic thermal self-healing behavior is directly visualized by scanning electron microscopy at 120 °C. This work demonstrates that combining dynamic Diels–Alder chemistry with solvent-free melt processing offers a practical and sustainable route to recyclable, reprocessable, and self-healable polyethylene materials with clear potential for large-scale industrial production. Full article

Guanidines are structurally unique, highly basic, nitrogen-containing organic compounds with strong hydrogen-bonding ability and biological activity, providing valuable functionality in medicinal chemistry, organocatalysis, and materials science. Among modern strategies for assembling guanidine-containing molecules, cycloaddition reactions have emerged as powerful tools due to their efficiency, stereoselectivity, and ability to rapidly build molecular complexity. Recent innovations have expanded cycloaddition methodologies for generating guanidine functionalities, incorporating guanidine-containing substrates, and using guanidine-based catalysts. This review summarizes these advances and highlights the current trends in guanidine-related cycloaddition chemistry. Full article

The cycloaddition reaction is one of the most common reactions in organic chemistry. It has been applied in various fields. Herein, we focus on the application of cycloaddition reactions in investigating biological molecules and materials using magnetic resonance techniques. To facilitate magnetic resonance studies such as electron paramagnetic resonance (EPR) spectroscopy and paramagnetic nuclear magnetic resonance (NMR) spectroscopy, there is often a requirement to attach spin labels and paramagnetic tags to the system of interest. The cycloaddition reaction is one of the ways to tether these spin labels and paramagnetic tags. In this review, we highlight the applications of various cycloaddition reactions such as the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the strain-promoted azide–alkyne cycloaddition (SPAAC) reaction and the Diels–Alder reaction in the interdisciplinary field of magnetic resonance studies of biomolecules, including proteins, nucleic acids, carbohydrates, lipids and glycans, as well as materials. Full article

Click chemistry is highly valued in the design of polymeric biomaterials due to its ability to generate complex structures and localized surface modifications. However, prominent mechanisms in click chemistry, such as copper-catalyzed azide-alkyne cycloaddition (CuAAC), are inefficient for the synthesis and/or modification of biomaterials because they present significant limitations for in vivo applications. The presence of residual copper in the material is toxic and requires extensive purification, increasing production costs and hindering scalability and availability for in vivo applications. To overcome these limitations and ensure the safety and biocompatibility of materials, biorthogonal reactions such as strain-promoted azide-alkyne cycloaddition (SPAAC) have been developed. Thiol-ene/thiol-yne and Diels–Alder mechanisms are also relevant for the formation of robust polymer networks with specific characteristics and attractive advantages for generating biocompatible materials. These reactions not only improve cell integration and reduce fibrosis in in vivo applications but also enable the creation of functional structures for tissue regeneration. This review provides a comprehensive analysis of advances in the synthesis of biomaterials for tissue regeneration using hydrogels designed via click chemistry, as well as the various mechanisms and structural considerations. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, demanding the continuous search for novel and more selective chemotherapeutic agents. Quinones, particularly naphthoquinones, constitute a privileged class of redox-active compounds with well-documented antitumor activity. Likewise, thiazoles represent a heterocyclic scaffold widely explored in medicinal chemistry due to their broad pharmacophoric adaptability and diverse biological activities. In this context, this review comprehensively explores the chemical synthesis and anticancer potential of hybrid molecules combining the naphthoquinone and thiazole scaffolds. The hybridization of these pharmacophores has emerged as a powerful strategy to design multitarget antitumor agents. The review summarizes key synthetic methodologies, including Hantzsch, hetero Diels–Alder cycloaddition and multicomponent reactions, leading to structurally diverse hybrids. Particular emphasis is placed on derivatives exhibiting strong cytotoxic effects against a broad spectrum of cancer cell lines (e.g., OVCAR3, MCF-7, A549, HCT-116, HeLa, and Jurkat), low toxicity toward normal cells and well-defined mechanisms of action involving topoisomerase IIα, EGFR, STAT3, and CDK1 inhibition, as well as ROS generation and cell cycle arrest. Among these, certain hybrids displayed nanomolar potency and high selectivity indices, reinforcing their potential as promising lead compounds for anticancer drug development. Full article

The multicomponent synthesis of a novel and highly symmetric polyheterocycle based on the pyrrolo[3,4-b]pyridin-5-one core incorporating the privileged tetrahydroisoquinoline moiety is described. The target compound was synthesized as an inseparable mixture of stereoisomers through a pseudo-repetitive Ugi–Zhu five-component reaction (PR-UZ-5CR) coupled to a double post-transformation sequence involving an intermolecular aza Diels–Alder cycloaddition, an intramolecular N-acylation, and a final tandem aromatization step. The product was prepared in 63% overall yield, and with an excellent atom economy of 85%, within a total reaction time of 85 min, and a temperature range from 25 to 65 °C. Structural elucidation and molecular mass confirmation were successfully achieved through NMR and FT-IR spectroscopy, and high-resolution mass spectrometry (HRMS), respectively. Full article

We investigated the Diels-Alder cycloaddition of methylcyclopentadiene with conjugated nitroalkenes and examined the influence of solvent polarity and substituent effects on the reaction mechanism. In nonpolar media (toluene), pathways A and C proceed via a pre-reactive molecular complex (MC), two transition states, and a heterocyclic intermediate, whereas pathways B and D follow a single-transition-state route directly to the norbornene product. Moderate increases in solvent polarity (acetone) do not qualitatively alter the energy profiles or mechanistic patterns, whereas highly polar solvents (methanol, acetonitrile, water, nitromethane) induce a fundamental transformation in pathway B, which adopts a stepwise, zwitterionic mechanism. NPA, MEP, and NCI analyses confirm the polar, charge-separated nature of the zwitterionic intermediate, while BET analysis elucidates the sequential electronic reorganization, highlighting early polarization toward the nitro fragment and stepwise formation of the C-C bonds. Substituent effect studies using Hammett σ parameters reveal that electron-withdrawing groups lower activation barriers, whereas electron-donating groups increase them, indicating that electronic effects dominate over steric factors. Overall, the study demonstrates a general, solvent- and substituent-dependent Diels-Alder mechanism, with pathway B proceeding through a polar, highly asynchronous, stepwise route involving a zwitterionic intermediate. Full article

Vinylallenes have been used in Diels–Alder reactions with a variety of dienophiles. However, vinylallenes activated at the allenic part of the molecule have been reacted only with carbon–carbon double bonds. We prepared siloxy vinylallenes by the base-induced equilibrium of silyl-protected allyl-propargyl alcohols. We found that these systems react with imines to form cycloadducts with total regio and facial selectivity, but only moderate endo:exo selectivity. The cycloadducts obtained were transformed into indolizidine derivatives. The reaction was studied computationally using DFT and compared to the reaction of siloxydienes. It was found that the main difference between those systems is the higher nucleophilicity of the siloxydienes compared to the siloxy vinylallenes. Full article