Diels-Alder Click Research Articles

Applications of Diels-Alder Chemistry in Biomaterials and Drug Delivery.

Recent studies, leveraging click chemistry reactions, have significantly advanced the fields of biomaterials and drug delivery. Of these click reactions, the Diels-Alder cycloaddition is exceptionally valuable for synthetic organic chemistry and biomaterial design, as it occurs under mild reaction conditions and can undergo a retrograde reaction, under physiologically relevant conditions, to yield the initial reactants. In this review, potential applications of the Diels-Alder reaction are explored within the nexus of biomaterials and drug delivery. This includes an emphasis on key platforms such as polymers, nanoparticles, and hydrogels which utilize Diels-Alder for drug delivery, functionalized surfaces, bioconjugation, and other diverse applications. Specifically, this review will focus on the use of Diels-Alder biomaterials in applications of tissue engineering and cancer therapies, while providing a discussion of the advantages, platforms, and applications of Diels-Alder click chemistry.

Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies.

Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels-Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.

A New Class of Mechano-Responsive PolyureThane Via Anthracene -TAD Diels-Alder (DA) Click Chemistry.

Smart or stimuli-responsive polymers have garnered significant interest in the scientific community due to their response to different stimuli like pH, temperature, light, mechanical force, etc. Mechanophoric polymer is an intriguing class of smart polymers that respond to external mechanical force by producing fluorescent moieties and can be utilized for damage detection and stress-sensing assessment. In recent reports on mechanophoric polymers, different mechanophoric motifs such as spiropyran, rhodamine, coumarin, etc. are explored. This investigation reports a new kind of mechanophoric polyurethane (PU) adduct based on Diels-Alder (DA) click chemistry. Here, an anthracene(An)-end capped tri-armed urethane system is synthesized, followed by a DA reaction using bis-(1,2,4-triazoline-3,5-dione) (bis-TAD) derivative. The incorporation of bis-TAD in the urethane system renders the anthracene inactive ("turn-off") by dismantling its conjugation as a result of a successful DA reaction. The soft PU translated into a harder material through bis-TAD linkages between polymer chains as evident from nanoindentation (NINT) analysis. The resulting material reverts back to its fluorescent "turned-on" mode owing to a force-accelerated retro-Diels-Alder (r-DA) reaction. Besides the mechanophoric attributes, the material demonstrates self-healing behavior examined by microscopic investigations. This innovative approach can be a potential route to design responsive polymers with dynamic functionalities for advanced material applications.

Bioorthogonal Diels-Alder Click Chemistry-Based Pretargeted PET Imaging Strategy for Monitoring Programmed Death-Ligand 1 Expression.

The development of antibody tracers for positron emission tomography (PET) imaging enables real-time monitoring of tumor expression of programmed cell death ligand 1 (PD-L1) in vivo, aiming to facilitate the selection of immunotherapy responders. However, the slow pharmacokinetics of the antibodies in vivo limits their applications in PET imaging with commonly used radionuclides with short half-lives. In this study, we developed a pretargeted PET imaging strategy based on Diels-Alder (IEDDA) click chemistry to overcome these limitations. Atezolizumab and durvalumab, the most commonly used PD-L1 antibodies in cancer immunotherapy, were selected and compared in the development of the pretargeted PET imaging strategy. Fluorine-18-labeled derivatives of methyl tetrazine ([18F]Tz, [18F]PEG6-Tz, and [18F]PEG12-Tz) were tested in biodistribution and PET imaging of A549-PDL1 xenografts (PD-L1 positive) pretargeted with the trans-cyclooctene (TCO)-functionalized atezolizumab/durvalumab. The biodistribution and imaging results indicated that atezolizumab-TCO/[18F]PEG12-Tz was more suitable for pretargeted PET imaging strategy, and the optimal interval time was 48 h after atezolizumab-TCO administration, where the atezolizumab-TCO/[18F]PEG12-Tz pretargeted approach clearly delineated the A549-PDL1 tumor with a tumor-to-muscle ratio of 5.33, while the ratios are 3.39 and 2.39 for durvalumab/[18F]PEG12-Tz and mock-pretargeting controls, respectively. In conclusion, a pretargeted 18F-immuno-PET imaging technology was successfully established on atezolizumab. The high-contrast PET images of the A549-PDL1 tumor models demonstrate that the pretargeting strategy incorporating short-lived fluorine-18 is viable in identifying tumors with high PD-L1 expression, marking this strategy as a potential candidate for further clinical translation.

Click Chemistry Enables [89Zr]Zr-DOTA Radioimmunoconjugation for Theranostic 89Zr-immunoPET.

There have been predictions that the use of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in zirconium-89 (89Zr) immuno-positron emission tomography (89Zr-immunoPET) could enhance the in vivo stability of 89Zr radioimmunoconjugates. However, conjugating [89Zr]Zr-DOTA to a monoclonal antibody (mAb) remains a challenge as the heat treatment required for [89Zr]Zr-DOTA chelation can lead to thermal denaturation of the mAb moieties. We developed a method for synthesizing [89Zr]Zr-DOTA-mAb based on a tetrazine (Tz)-conjugated bifunctional DOTA derivative 2,2',2″-(10-(1-(4-(1,2,4,5-tetrazin-3-yl)phenyl)-3,21,26-trioxo-6,9,12,15,18-pentaoxa-29-carboxy-2,22,25-triazanonacosane-29-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-Tz) and the inverse electron-demand Diels-Alder (IEDDA) click chemistry reaction where trans-cyclooctene-modified mAbs are conjugated to [89Zr]Zr-DOTAGA without being exposed to heat. The stability of IEDDA-derived [89Zr]Zr-DOTAGA-trastuzumab was confirmed by in vitro, ex vivo, and in vivo testing and comparative analysis against the conventional deferoxamine (DFO) counterpart [89Zr]Zr-DFO-trastuzumab. The in vivo immunoPET imaging using [89Zr]Zr-DOTAGA-trastuzumab clearly visualized human epidermal growth factor receptor 2-positive malignancies in murine xenograft models. Greater tumor contrast was observed from [89Zr]Zr-DOTAGA-trastuzumab at a 72-h delayed scan compared with [89Zr]Zr-DFO-trastuzumab. These findings suggest that our IEDDA ligation approach can be an effective means of synthesizing [89Zr]Zr-DOTA-mAb and can enhance the theranostic potential of 89Zr-immunoPET in DOTA-mediated radioimmunotherapy.

The Topological Transformation of Trefoil Knots to Solomon Links via Diels-Alder Click Reaction.

The quest for more efficient, user-friendly, and less wasteful topological transformations remains a significant challenge in the realm of postassembly modifications. In this article, high yields of two molecular trefoil knots (Rh-1, Ir-1) were obtained using ligand 3,6-bis(3-(pyridin-4-yl)phenyl)-1,2,4,5-tetrazine (L1) with reactive tetrazine units and binuclear half-sandwich organometallic units [Cp*2M2(μ-TPPHZ)(OTf)2](OTf)2 (Rh-B, M = RhIII; Ir-B, M = IrIII). 2,5-Norbornadiene was used as an inducer of the Diels-Alder click reaction to modulate rapidly and efficiently the transformation of Trefoil knots to Solomon links. However, the key to achieving this topological structural change is the subtle increase in site steric of the pyridazine fragments (L2), which allows the molecular structures to spread and bend in three-dimensional space, as confirmed by single-crystal X-ray diffraction, ESI-TOF/MS, elementary analysis and detailed solution-state NMR techniques.

Minimally invasive delivery of human umbilical cord-derived mesenchymal stem cells by an injectable hydrogel via Diels–Alder click reaction for the treatment of intrauterine adhesions

Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. Statement of significanceSevere endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.

Triple click chemistry for crosslinking, stiffening, and annealing of gelatin-based microgels.

Microgels are spherical hydrogels with physicochemical properties ideal for many biomedical applications. For example, microgels can be used as individual carriers for suspension cell culture or jammed/annealed into granular hydrogels with micron-scale pores highly permissive to molecular transport and cell proliferation/migration. Conventionally, laborious optimization processes are often needed to create microgels with different moduli, sizes, and compositions. This work presents a new microgel and granular hydrogel preparation workflow using gelatin-norbornene-carbohydrazide (GelNB-CH). As a gelatin-derived macromer, GelNB-CH presents cell adhesive and degradable motifs while being amenable to three orthogonal click chemistries, namely the thiol-norbornene photo-click reaction, hydrazone bonding, and the inverse electron demand Diels-Alder (iEDDA) click reaction. The thiol-norbornene photo-click reaction (with thiol-bearing crosslinkers) and hydrazone bonding (with aldehyde-bearing crosslinkers) were used to crosslink the microgels and to realize on-demand microgel stiffening, respectively. The tetrazine-norbornene iEDDA click reaction (with tetrazine-bearing crosslinkers) was used to anneal microgels into granular hydrogels. In addition to materials development, we demonstrated the value of the triple-click chemistry granular hydrogels via culturing human mesenchymal stem cells and pancreatic cancer cells.

Orthogonally Crosslinked Gelatin-Norbornene Hydrogels for Biomedical Applications.

The thiol-norbornene photo-click reaction has exceptionally fast crosslinking efficiency compared with chain-growth polymerization at equivalent macromer contents. The orthogonal reactivity between norbornene and thiol/tetrazine permits crosslinking of synthetic and naturally derived macromolecules with modularity, including poly(ethylene glycol) (PEG)-norbornene (PEGNB), gelatin-norbornene (GelNB), among others. For example, collagen-derived gelatin contains both cell adhesive motifs (e.g., Arg-Gly-Asp or RGD) and protease-labile sequences, making it an ideal macromer for forming cell-laden hydrogels. First reported in 2014, GelNB is increasingly used in orthogonal crosslinking of biomimetic matrices in various applications. GelNB can be crosslinked into hydrogels using multi-functional thiol linkers (e.g., dithiothreitol (DTT) or PEG-tetra-thiol (PEG4SH) via visible light or longwave ultraviolet (UV) light step-growth thiol-norbornene reaction or through an enzyme-mediated crosslinking (i.e., horseradish peroxidase, HRP). GelNB-based hydrogels can also be modularly crosslinked with tetrazine-bearing macromers via inverse electron-demand Diels-Alder (iEDDA) click reaction. This review surveys the various methods for preparing GelNB macromers, the crosslinking mechanisms of GelNB-based hydrogels, and their applications in cell and tissue engineering, including crosslinking of dynamic matrices, disease modeling, and tissue regeneration, delivery of therapeutics, as well as bioprinting and biofabrication.

Reprocessable thermal interface materials with optimized phonon transport based on Diels-Alder click chemistry

Reprocessable thermal interface materials with optimized phonon transport based on Diels-Alder click chemistry

Trans-Cyclooctene- and Bicyclononyne-Linked Nucleotides for Click Modification of DNA with Fluorogenic Tetrazines and Live Cell Metabolic Labeling and Imaging.

A series of 2'-deoxyribonucleoside triphosphates (dNTPs) bearing 2- or 4-linked trans-cyclooctene (TCO) or bicyclononyne (BCN) tethered through a shorter propargylcarbamate or longer triethyleneglycol-based spacer were designed and synthesized. They were found to be good substrates for KOD XL DNA polymerase for primer extension enzymatic synthesis of modified oligonucleotides. We systematically tested and compared the reactivity of TCO- and BCN-modified nucleotides and DNA with several fluorophore-containing tetrazines in inverse electron-demand Diels-Alder (IEDDA) click reactions to show that the longer linker is crucial for efficient labeling. The modified dNTPs were transported into live cells using the synthetic transporter SNTT1, incubated for 1 h, and then treated with tetrazine conjugates. The PEG3-linked 4TCO and BCN nucleotides showed efficient incorporation into genomic DNA and good reactivity in the IEDDA click reaction with tetrazines to allow staining of DNA and imaging of DNA synthesis in live cells within time periods as short as 15 min. The BCN-linked nucleotide in combination with TAMRA-linked (TAMRA = carboxytetramethylrhodamine) tetrazine was also efficiently used for staining of DNA for flow cytometry. This methodology is a new approach for in cellulo metabolic labeling and imaging of DNA synthesis which is shorter, operationally simple, and overcomes several problems of previously used methods.

Synthesis and thermal-responsive behavior of a polysiloxane-based material by combined click chemistries

A thermally reversible and high performance polydimethylsiloxane (PDMS)-based network was easily achieved from a novel single molecular silicone-based Diels–Alder crosslinker, which was obtained via the combination of the thiol-acrylate Michael addition and Diels-Alder click chemistries in a straightforward one-pot fashion. The high flexibility of the silicone-derived crosslinker allows for good healing of complete cuts without the need of a pre-healing step to dissociate the dynamic DA bonds. The cut healing process was possible via a single heating step at 70 °C, reaching a relatively good healing efficiency, evaluated by a tensile strength recovery of above 80%.

Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels-Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications.

Microfluidic on-chip production of polymeric hydrogel microspheres (MPs) can be designed for the loading of different biologically active cargos and living cells. Among different gelation strategies, ionically crosslinked microspheres generally show limited mechanical properties, meanwhile covalently crosslinked microspheres often require the use of crosslinking agents or initiators with limited biocompatibility. Inverse electron demand Diels Alder (iEDDA) click chemistry is a promising covalent crosslinking method with fast kinetics, high chemoselectivity, high efficiency and no cross-reactivity. Herein, in situ gellable iEDDA-crosslinked polymeric hydrogel microspheres are developed via water-in-oil emulsification (W/O) glass microfluidics. The microspheres are composed of two polyethylene glycol precursors modified with either tetrazine or norbornene as functional moieties. Using a single co-flow glass microfluidic platform, homogenous MPs of sizes 200-600 μm are developed and crosslinked within 2 minutes. The rheological properties of iEDDA crosslinked bulk hydrogels are maintained with a low swelling degree and a slow degradation behaviour under physiological conditions. Moreover, a high-protein loading capacity can be achieved, and the encapsulation of mammalian cells is possible. Overall, this work provides the possibility of developing microfluidics-produced iEDDA-crosslinked MPs as a potential drug vehicle and cell encapsulation system in the biomedical field.

Optimizing and determining the click chemistry mediated Cu-64 radiolabeling and physiochemical characteristics of trastuzumab conjugates

Over the last decade, 64Cu-labeling of monoclonal antibody (mAb) via inverse electron demand Diels-Alder click chemistry (IEDDA) have received much attention. Despite the tetrazine-transcyclooctene (Tz-TCO) click chemistry's convenience and efficiency in mAb labeling, there is limited information about the ideal parameters in the development of click chemistry mediated (radio)immunoconjugates. This encourages us to conduct a systematic optimization while concurrently determining the physiochemical characteristics of the model mAb, trastuzumab, and TCO conjugates. To accomplish this, we investigated a few critical parameters, first, we determined the degree of conjugations with varying molar equivalents (eq.) of TCO (3, 5, 10, and 15 eq.). Through analytical techniques like size exclusion chromatography, dynamic light scattering, and zeta potential, qualitative analysis were performed to determine the purity, degree of aggregation and net charge of the conjugates. We found that as the degree of conjugation increased the purity of intact mAb fraction is compromised and net charge of conjugates became less positive. Next, all trastuzumab-PEG4-TCO conjugates with varying molar ratio and quantity (30, 50, 100, 200, 250 μg) were radiolabeled with 64Cu-NOTA-PEG4-Tz via IEDDA click chemistry and radiochemical yields were determined by radio-thin layer chromatography. The radiochemical yields of trastuzumab conjugates improved with increased amount and molar ratio. Next, we investigated the effect of the radioprotectant ascorbic acid (AA) of varied concentrations (0.25, 0.5, 0.75, 1 mM) on radiochemical yields and subsequent pharmacokinetics. A concentration of 0.25 mM of AA was found to be optimal for click reaction and in vivo biodistribution. Finally, we investigated the indirect influence of bioconjugation buffers on radiochemical yields and biodistribution in NIH3T6.7 tumor models that resulted approximately ∼11 %ID/g tumor uptake.

Bio-orthogonal Toolbox for Monitoring Nitric Oxide in Targeted Organelles of Live Cells and Zebrafishes.

Nitric oxide (NO), playing crucial roles as a cellular messenger and as a toxic ROS, is highly related to the physiological and pathological states of living systems. The very wide but very uneven distribution of this radical gas in the inhomogeneous biological microenvironment imposes big challenges for specifically detecting its local level in certain subcellular areas, which calls for a long list of NO probes for each target. In order to simplify the syntheses and designs of these probes, herein it is proposed to construct a versatile NO-sensing toolbox based on a bio-orthogonal concept, i.e., inverse electron demand Diels-Alder click reaction between tetrazine and strained alkyne BCN. On the one hand, rhodamine-o-phenylenediamine as the NO-responsive scaffold is coupled with a tetrazine unit to generate a general probe TMR-Tz-NO, which, to our knowledge, is the first case of the tetrazine-coupled analyte-responsive probe. On the other hand, the BCN moiety is connected to different targeting groups, such as TPP, morpholine, and Ac4ManN, targeting to mitochondria, lysosomes, and membranes, respectively. It works well to use TMR-Tz-NO to match with any targetable BCN counterpart in this toolbox to achieve the imaging of NO in the corresponding subcellular area. For example, through metabolism, Ac4ManN-BCN is effectively taken and grows on the cell membranes. The bio-orthogonal reaction between TMR-Tz-NO and Ac4ManN-BCN makes the NO probe anchored to the membrane surface permanently. The zebrafish experiment revealed that this bio-orthogonal pair can track and image the NO produced during inflammation in vivo.

Gradual hydrogel degradation for programable repairing full-thickness skin defect wound

Full-thickness skin defect wound infection seriously threatens the life and health of patients. Highly efficient antibacterial activity and angiogenesis after injury are critical for the wound healing process. In this work, we first designed various of halogen-free imidazolium poly(ionic liquids) (PILs) as the antibacterial agents, and selected the highest efficient antibacterial PIL. Then, we fabricated hyaluronic acid/poly(ethylene glycol)/PILs semi interpenetrating polymer network (semi-IPN) wound dressings by Diels-Alder (DA) click reaction, and deferoxamine (DFO) which promoted angiogenesis was grafted into the hydrogel wound dressings. In vitro and in vivo assays respectively evaluated the fast antibacterial property of the hydrogels against Escherichia coli and Staphylococcus aureus at skin infected wound areas. With the hydrogels enzymatic degradation by hyaluronidase, the degradation solution could reduce inflammation, promote angiogenesis and wound healing due to the continuous releasing of DFO and PIL. The programable hydrogel degradation protocol provided a new strategy for rapid full-thickness skin defect wound healing in the clinic application.

Pretargeted PET of Osteodestructive Lesions in Dogs.

The last decade has witnessed the creation of a highly effective approach to in vivo pretargeting based on the inverse electron demand Diels-Alder (IEDDA) click ligation between tetrazine (Tz) and trans-cyclooctene (TCO). Despite the steady progression of this technology toward the clinic, concerns have persisted regarding whether this in vivo chemistry will work in humans given their larger size and blood volume. In this work, we describe the use of a 64Cu-labeled Tz radioligand ([64Cu]Cu-SarAr-Tz) and a TCO-bearing bisphosphonate (TCO-BP) for the pretargeted positron emission tomography (PET) imaging of osteodestructive lesions in a large animal model: companion dogs. First, in a small animal pilot study, healthy mice were injected with TCO-BP followed after 1 or 6 h by [64Cu]Cu-SarAr-Tz. PET images were collected 1, 6, and 24 h after the administration of [64Cu]Cu-SarAr-Tz, revealing that this approach produced high activity concentrations in the bone (>20 and >15%ID/g in the femur and humerus, respectively, at 24 h post injection) as well as high target-to-background contrast. Subsequently, companion dogs (n = 5) presenting with osteodestructive lesions were administered TCO-BP (5 or 10 mg/kg) followed 1 h later by [64Cu]Cu-SarAr-Tz (2.2-7.3 mCi; 81.4-270.1 MBq). PET scans were collected for each dog 4 h after the administration of the radioligand, and SUV values for the osteodestructive lesions, healthy bones, and kidneys were determined. In these animals, pretargeted PET clearly delineated healthy bone and produced very high activity concentrations in osteodestructive lesions. Low levels of uptake were observed in all healthy organs except for the kidneys and bladder due to the renal excretion of excess radioligand. Ultimately, this work not only illustrates that pretargeted PET with TCO-BP and [64Cu]Cu-SarAr-Tz is an effective tool for the visualization of osteodestructive lesions but also demonstrates for the first time that in vivo pretargeting based on IEDDA click chemistry is feasible in large animals.

Designing End-of-Life Recyclable Polymers via Diels-Alder Chemistry: A Review on the Kinetics of Reversible Reactions.

The purpose of this review is to critically assess the kinetic behavior of the furan/maleimide Diels-Alder click reaction. The popularity of this reaction is evident and still continues to grow, which is likely attributed to its reversibility at temperatures above 100°C, and due to its biobased "roots" in terms of raw materials. This chemistry is used to form thermoreversible crosslinks in polymer networks, and thus allows the polymer field to design strong, but also end-of-life recyclable thermosets and rubbers. In this context, the rate at which the forward reaction (Diels-Alder for crosslinking) and its reverse (retro Diels-Alder for decrosslinking) proceed as a function of temperature is of crucial importance in assessing the feasibility of the design in real-life products. Differences in kinetics based from various studies are not well understood, but are potentially caused by chemical side groups, mass transfer limitations, and the analysis methods being employed. In this work, all the relevant studies are attempted to be placed in perspective with respect to each other, and thereby offer a general guide is offered on how to assess their recycling kinetics.

Preparation of ferrocenyl-furan modified graphene oxide via Diels-Alder click reaction and using of its polypyrrole nanocomposites as supercapacitor electrode material

In the present study, the 1-(2-furyl)acryloylferrocene was prepared as a suited scaffold for Diels–Alder reaction with graphene oxide. In order to increasing of conductivity, the ferrocenyl functionalized graphene oxide (GO-FcFu) was physically mixed with polypyrrole. Polypyrrole as an organic polymer was obtained by oxidative polymerization of pyrrole. The obtained GO-FcFu/PPy nanocomposite were tested as hybrid supercapacitor with dual features of electrical double layer capacitance and pseudocapacitive arising from GO and ferrocene species, respectively. The improved surface area (33.41 m2 g−1), high mass specific capacity of 231.31 mAh g−1 (1 A g−1), and the capacity retains 89% of initial capacity after 5000 cycles were estimated the sufficiency of final composite for use as electrode material.

Poly(ε‐caprolactone)/montmorillonite nanocomposites via Diels–Alder click reaction

AbstractSynthesis of nanocomposites by employing inorganic materials as nanofillers is one of the most effective ways to improve the mechanical and thermal properties of conventional polymers. To design and create new nanomaterials with unprecedented functional attributes, the fabrication techniques and chemistries employed often have utmost importance to attain a better structure–property relationship. In this respect, click chemistry‐based functional methodologies hold great promise in the fabrication of polymeric nanocomposites due to their excellent features. In this contribution, poly(ε‐caprolactone)/clay nanocomposites were prepared by Diels–Alder (DA) click reaction of maleimide end‐group containing poly(ε‐caprolactone) and furan functionalized montmorillonite (MMT). The methodology includes furan modification of MMT clay and ring‐opening polymerization of ε‐caprolactone that was initiated with a masked maleimide group containing alcohol and following retro DA reaction to obtain maleimide end group functional poly(ε‐caprolactone). Subsequently, polymer nanocomposites were efficiently fabricated via DA click reaction of functional poly(ε‐caprolactone) polymer and modified clay in thermal heating conditions at 80°C. The characterization of poly(ε‐caprolactone)/clay nanocomposites was carried out by thermogravimetric analysis, Fourier transform‐infrared spectroscopy, X‐ray diffraction spectroscopy, and transmission electron microscopy. Obtained results demonstrated that DA click reaction can be fruitfully employed in the fabrication of MMT‐based polymeric nanocomposites.