Search Results (74)

Polycyclic aromatic compounds can often be made by a sequence featuring an initial Diels–Alder [4 + 2] cycloaddition reaction, followed by cheletropic extrusion of carbon monoxide. These reactions normally require heating the diene and dieneophile in petrochemical-derived aromatic hydrocarbon solvents, such as xylenes or diphenyl ether. This article summarizes the results of attempts to use renewable solvents in place of those currently in use to prepare pentaphenylbenzene and 1,2,4-triphenyltriphenylene. Dihydrolevoglucosenone, p-cymene, ethyl lactate, diethyl carbonate, and cyclopentyl methyl ether have all been successfully evaluated as renewable solvent alternatives in Diels–Alder/cheletropic reaction sequences. An analysis of the products from the reactions investigated did not show evidence of oxidative degradation of the diene reactants. Furthermore, norbornadien-7-one intermediates were not isolated from any of the reactions tested. Full article

In the chemistry of bio-based furans, the Diels–Alder reaction plays an important role as a renewable route for the synthesis of fuels, fine chemicals, and monomers. Nonetheless, the unfavorable kinetic and thermodynamic parameters inherent to the Diels–Alder reaction involving furans as dienes often lead to the reversibility of cycloaddition, resulting in decreased equilibrium conversion and diastereoselectivity. In this study, we present a new strategy for overcoming the problem of reversibility in chemical reactions. We demonstrate that conducting the reaction under solvent-free conditions can facilitate the transition from a molten state formed by the initial reactants to a solid phase containing the reaction product along with an excess of the initial substrate. According to our results, such a liquid-to-solid transition of the reaction mixture can lead to exceptionally high conversion and diastereoselectivity in the furan–maleimide Diels–Alder reaction, particularly for challenging electron-poor furanic substrates. Our approach enables the reversible furan–maleimide Diels–Alder reaction to be performed in a cleaner and more environmentally friendly manner, free from the complexities associated with the use of solvents and the need for purification from side products. Full article

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 10⁴ – 2.26 × 10⁴ g/mol and Mw = 2.90 × 10⁴–3.05 × 10⁴ g/mol with good polydispersity, Đ_M = 1.32–1.35, and excellent thermal stability (up to 309°C T_d10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain. Full article

This study introduces an efficient and scalable method for the top-down exfoliation of graphite into graphite nanoplatelets (GNPs) using polyketones (PKs) functionalized with Diels–Alder (DA) active groups. Leveraging the reversible covalent interactions facilitated by furan and thiophene moieties in PK, combined with melt-mixing and shear force, this process achieves significant exfoliation while preserving the structural integrity of the resulting material. Thermal and rheological analyses demonstrate enhanced interfacial adhesion and stability within polymer composites attributed to the DA-driven interactions between functionalized PK and graphite. Comparative evaluations demonstrate that furan-functionalized PK exhibits superior exfoliation efficiency, highlighting its potential for producing high-quality exfoliated graphite suitable for advanced nanocomposite applications that require enhanced thermal, mechanical, and electrical properties. This method seamlessly integrates sustainability with industrial scalability, offering significant advancements in developing GNP-based materials. Full article

Chitosan (CS), a versatile biopolymer obtained through the deacetylation of chitin, has gained significant interest in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, and unique gel-forming capabilities. This review comprehensively analyzes CS-based gel development, covering its extraction from various natural sources, gelation mechanisms, and biomedical applications. Different extraction methods, including chemical, biological, and green techniques, are discussed regarding efficiency and sustainability. The review explores the physicochemical properties of CS that influence its gelation behavior, highlighting various gelation mechanisms such as physical, ionic, and chemical cross-linking. Recent advances in gel formation, including Schiff base reactions, Diels–Alder click chemistry, and thermosensitive gelation, have expanded the applicability of CS hydrogels. Furthermore, CS-based gels have demonstrated potential in wound healing, tissue engineering, drug delivery, and antimicrobial applications, offering controlled drug release, enhanced biocompatibility, and tunable mechanical properties. The incorporation of nanomaterials, bioactive molecules, and functional cross-linkers has further improved hydrogel performance. The current review underscores the growing significance of CS-based gels as innovative biomaterials in regenerative medicine and pharmaceutical sciences. Full article

Furan/maleimide dynamic covalent chemistry has been extensively used to fabricate re-workable and self-healing thermosets. Understanding the relationship between crosslinker structure, network dynamics, and material final properties, however, remains a challenge. This study introduces self-healing and shape-memory thermosets derived from furan-functionalized polyketones (PKFU) crosslinked with aromatic bis-maleimides, i.e., 1,1′-(methylenedi-4,1-phenylene)bis-maleimide (BISM1) and bis(3-ethyl-5-methyl-4-maleimidophenyl)methane (BISM2), via a thermally reversible Diels-Alder reaction. Polyketones were chemically modified with furfurylamine through the Paal-Knorr reaction, achieving varying furan grafting ratios. The resulting networks, characterized by ATR-FTIR, ¹H-NMR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and rheology, demonstrated tunable thermomechanical properties. BISM2-based thermosets exhibited enhanced thermal stability and reversibility over a broad temperature range (20–120 °C), with a shape recovery ratio of up to 89% and complete self-healing at 120 °C within 5 min. These findings highlight the potential of polyketone-based thermosets for applications requiring adaptive thermomechanical properties, efficient self-repair, and sustainability. Full article

An ultrasound-responsive hydrogel system was developed that provides on-demand release when stimulated by focused ultrasound (fUS). Diels–Alder cycloadducts crosslinked polyethylene glycol (PEG) hydrogels and underwent a retrograde Diels–Alder reaction when exposed to fUS. Four-arm and eight-arm furan-based Diels–Alder hydrogel compositions were used to evaluate the link between the crosslinking density and the fUS-induced release and retention rates. PEG crosslinked with glutaraldehyde was also used as a non-Diels–Alder control hydrogel. By increasing the exposure time and the amplitude of fUS, the Diels–Alder-based hydrogels exhibited a correlative increase in the release of the entrapped BMP-2. Real-time B-mode imaging was used during fUS to visualize the on-demand degradation of the crosslinking matrix for the release of BMP-2. When monitored with a thermocouple, the increase in temperature observed was minimal in the area surrounding the sample during fUS stimulation, indicating fUS to be an external stimulus which could be used safely for spatiotemporally controlled release. PEG hydrogels were characterized using nuclear magnetic resonance, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and compression testing. PEG degradation byproducts were evaluated for cytocompatibility in vitro. Overall, this study demonstrated that Diels–Alder-based PEG hydrogels can encapsulate BMP-2, undergo a retrograde reaction when externally stimulated with fUS, and release active BMP-2 to induce differentiation in human mesenchymal stem cells. Full article

Since its conceptualization, click chemistry in all its variants has proven to be a superior synthesis protocol, compared to conventional methods, for forming new covalent bonds under mild conditions, orthogonally, and with high yields. If a term like reactive resilience could be established, click reactions would be good examples, as they perform better under increasingly challenging conditions. Particularly, highly hindered couplings that perform poorly with conventional chemistry protocols—such as those used to conjugate biomacromolecules (e.g., proteins and aptamers) or multiple drugs onto macromolecular platforms—can be more easily achieved using click chemistry principles, while also promoting high stereoselectivity in the products. In this review, three molecular platforms relevant in the field of nanomedicine are considered: polymers/copolymers, cyclodextrins, and fullerenes, whose functionalization poses a challenge due to steric hindrance, either from the intrinsic bulk behavior (as in polymers) or from the proximity of confined reactive sites, as seen in cyclodextrins and fullerenes. Their functionalization with biologically active groups (drugs or biomolecules), primarily through copper-catalyzed azide–alkyne cycloaddition (CuAAC), strain-promoted azide–alkyne cycloaddition (SPAAC), inverse electron-demand Diels–Alder (IEDDA) and thiol–ene click reactions, has led to the development of increasingly sophisticated systems with enhanced specificity, multifunctionality, bioavailability, delayed clearance, multi-targeting, selective cytotoxicity, and tracking capabilities—all essential in the field of nanomedicine. Full article

Ψ-1,4-naphthoquinones (Ψ-NQ) are non-quinoid compounds in which aromaticity—found in 1,4-naphthoquinones—is broken by the introduction of an angular methyl at C-4a or -8a. This series was designed to act as prodrugs of 1,4-naphthoquinones in an oxidative environment. Furthermore, from a medicinal chemistry point of view, the loss of planarity of the scaffold might lead to an improved solubility and circumvent the bad reputation of quinones in the pharmaceutical industry. In this work, we illustrated the concept by the synthesis of Ψ -plasmodione regioisomers as prodrugs of the antimalarial plasmodione. The presence of a chiral center introduces a new degree of freedom to be controlled by enantioselectivity and regioselectivity of the cycloaddition in the Diels–Alder reaction. The first strategy that was followed was based on the use of a chiral enantiopure sulfoxide to govern the stereoselective formation of (+)Ψ-NQ or (−)Ψ-NQ, depending on the chirality of the sulfoxide (R or S). New sulfinylquinones were synthesized but were found to be ineffective in undergoing cycloaddition with different dienes under a wide range of conditions (thermal, Lewis acid). The second strategy was based on the use of boronic acid-substituted benzoquinones as auxiliaries to control the regioselectivity. Using this methodology to prepare the (±)Ψ-NQ racemates, promising results (very fast cycloaddition time: ~2 h) were obtained with boronic acid-based quinones 25 and 27 in the presence of 1-methoxy-1,3-butadiene, to generate the 4a- and the 8a-Ψ-plasmodione regioisomers 1 and 2 (synthesized in six steps with a total yield of 10.5% and 4.1%, respectively. As the expected prodrug effect can only be revealed if the molecule undergoes an oxidation of the angular methyl, e.g., in blood-feeding parasites that digest hemoglobin from the host, the antimalarial and the antischistosomal properties of both (±)Ψ-NQ regioisomers were determined in drug assays with Plasmodium falciparum and Schistosoma mansoni. Metabolic studies under quasi-physiological conditions and LC-MS analyses were undertaken to reveal the generation of plasmodione from both the 4a- and the 8a-Ψ-plasmodione regioisomers. Full article

Background: The incorporation of radionuclides into peptides and larger biomolecules requires efficient and sometimes biorthogonal reaction conditions, to which click chemistry provides a convenient approach. Methods: Traditionally, click-based radiolabeling techniques have focused on classical click chemistry, such as copper(I)-catalyzed alkyne-azide [3+2] cycloaddition (CuAAC), strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), traceless Staudinger ligation, and inverse electron demand Diels–Alder (IEDDA). Results: However, newly emerging click-based radiolabeling techniques, including tyrosine-click, sulfo-click, sulfur(VI) fluoride exchange (SuFEx), thiol-ene click, azo coupling, hydrazone formations, oxime formations, and RIKEN click offer valuable alternatives to classical click chemistry. Conclusions: This review will discuss the applications of these techniques in peptide radiochemistry. Full article

With the background of the fossil fuel energy crisis, the development of self-healing and recyclable polymer materials has become a research hotspot. In this work, a kind of cross-linking agent with pendent furan groups was first prepared and then used to produce the Polyurethane elastomer based on Diels–Alder chemistry (EPU–DA). In addition, in order to further enhance the mechanical properties of the elastomer, cellulose nanofibers (CNFs) were added into the Polyurethane system to prepare a series of composites with various contents of CNF (wt% = 0.1~0.7). Herein, the FTIR and DSC were used to confirm structure and thermal reversible character. The tensile test also indicated that the addition of CNF increased the mechanical properties compared to the pure Polyurethane elastomer. Due to their reversible DA covalent bonds, the elastomer and composites were recycled under high-temperature conditions, which extends Polyurethane elastomers’ practical applications. Moreover, damaged coating can also be repaired, endowing this Polyurethane material with good potential for application in the field of metal protection. Full article

An investigation of phenolic glycosides extracted from Salix germplasm revealed that arbusculoidin (benzyl 1-O-β-d-glucopyranosyl-1-hydroxy-6-oxo-2-cyclohexenyl carboxylate) and its enolic 6-glycoside isomer, isoarbusculoidin, are widespread across the Salix family. An analysis of natural hybrid species and progeny from a willow breeding programme demonstrated that the putative biosynthetic pathway leading to the salicinoid family of phenolic glycosides runs in parallel to a “benzyl”-based pathway to arbusculoidin. The introduction of a known Diels–Alder reaction trait from Salix dasyclados, as well as an acylation trait, into progeny containing both salicyl- and benzyl- pathways caused the formation of all possible hetero-cyclodimers from mixtures of reactive dienone (acyl)glycosides that participated in cross-over reactions. In addition to providing access to new analogues of the anti-cancer dimer miyabeacin, the analysis of the breeding progeny also indicated that these dienone (acyl)glycosides are stable in planta. Although the immediate biosynthetic precursors of these compounds remain to be defined, the results suggest that the (acyl)glycosylation reactions may occur later in the pathway than previously suggested by in vitro work on cloned UGT enzymes. Full article

The Diels–Alder equilibrium is a widely known process in chemistry that can be used to provide a thermoset structure with recyclability and reprocessability mechanisms. In this study, a commercial epoxy resin is modified through the integration of functional groups into the network structure to provide superior performance. The present study has demonstrated that it is possible to adapt the curing process to efficiently incorporate these moieties in the final structure of commercial epoxy-based resins. It also evaluates the impact that they have on the final properties of the cured composites. In addition, different approaches have been studied for the incorporation of the functional group, adjusting and adapting the stoichiometry of the system components due to the differences in reactivity caused by the presence of the incorporated reactive groups, with the objective of maintaining comparable ratios of epoxy/amine groups in the formulation. Finally, it has been demonstrated that although the Diels–Alder equilibrium responds under external conditions, such as temperature, different sets of parameters and behaviors are to be expected as the structures are integrated into the thermoset, generating new equilibrium temperatures. In this way, the present research has explored sustainable strategies to enable the recyclability of commercial thermoset systems through crosslinking control and its modification. Full article

The chemistry of conjugated nitrodienes is becoming increasingly popular. These molecules are successfully applied in cycloaddition to synthesize six-membered rings in Diels-Alder reactions. Nitrodienes can be also applied to obtain bis-compounds in [3+2] cycloaddition. Moreover, the presence of a nitro group in the structure provides a possibility of further modification of the products. The simplest symmetrical representative of conjugated nitrodienes is (1E,3E)-1,4-dinitro-1,3-butadiene. Although the first mentions of the compound date back to the early 1950s, the compound has not yet been examined thoroughly enough. Therefore, in this article, a comprehensive study of (1E,3E)-1,4-dinitro-1,3-butadiene has been described. For this purpose, an experimental study including the synthesis process as well as an evaluation of the spectral characteristics has been conducted. So as to better understand the properties of this compound, a computational study of reactivity indices based on MEDT and also an assessment of pharmacokinetics and biological activity according to ADME and PASS methodologies have been made. On this basis, some future application trends of (1E,3E)-1,4-dinitro-1,3-butadiene have been proposed. Full article

Covalent adaptable networks (CANs) represent a pioneering advance in polymer science, offering unprecedented versatility in materials design. Unlike conventional adhesives with irreversible bonds, CAN-based polyurethane adhesives have the unique ability to undergo chemical restructuring through reversible bonds. One of the strategies for incorporating these types of reactions in polyurethanes is by functionalisation with Diels–Alder (DA) adducts. By taking advantage of the reversible nature of the DA chemistry, the adhesive undergoes controlled crosslinking and decrosslinking processes, allowing for precise modulation of bond strength. This adaptability is critical in applications requiring reworkability or recyclability, as it allows for easy disassembly and reassembly of bonded components without compromising the integrity of the material. This study focuses on the sustainable synthesis and characterisation of a solvent-based polyurethane adhesive, obtained by functionalising a polyurethane prepolymer with DA diene and dienophiles. The characterisation of the adhesives was carried out using different experimental techniques: nuclear magnetic resonance spectroscopy (NMR), Brookfield viscosity, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and T-peel strength testing of leather/adhesive/rubber joints to determine the adhesive properties, both before and after the application of external stimuli. The conversion of both the DA and retro-Diels–Alder (r-DA) reactions was confirmed by ¹H-NMR. The adhesive properties were not altered by the functionalisation of the adhesive prepolymer, showing similar thermal resistance and good rheological and adhesive properties, even exceeding the most demanding technical requirements for upper-to-sole joints in footwear. After the application of an external thermal stimuli, the bonded materials separated without difficulty and without damage, thus facilitating their separation, recovery and recycling. Full article