Asymmetric Synthesis of Three Alkenyl Epoxides: Crafting the Sex Pheromones of the Elm Spanworm and the Painted Apple Moth.

A concise synthesis of the sex pheromones of elm spanworm as well as painted apple moth has been achieved. The key steps were the alkylation of acetylide ion, Sharpless asymmetric epoxidation and Brown's P2-Ni reduction. This approach provided the sex pheromone of the elm spanworm (1) in 31% total yield and those of the painted apple moth (2, 3) in 26% and 32% total yields. The ee values of three final products were up to 99%. The synthesized pheromones hold promising potential for use in the management and control of these pests.

Construction of Polycarbonates with Pendant Multifunctional Groups via a One-Step CO2/ Diepoxide Copolymerization Approach.

A "one-step" strategy has been demonstrated for the tunable synthesis of multifunctional aliphatic polycarbonates (APCs) with ethylene oxide (EO), ethylene carbonate (EC), and cyclohexene oxide (CHO) side groups by the copolymerization of 4-vinyl-1-cyclohexene diepoxide with carbon dioxide under an aminotriphenolate iron/PPNBz (PPN = bis(triphenylphosphine)-iminium, Bz = benzoate) binary catalyst. By adjusting the PPNBz-to-iron complex ratio and incorporating auxiliary solvents, the content of functional side groups can be tuned within the ranges of 53-75% for EO, 18-47% for EC, and <1-7% for CHO. The yield and molecular weight distribution of the resulting multifunctional APCs are affected by the viscosity of the polymerization system. The use of tetrahydrofuran as an auxiliary solvent enables the preparation of narrow-distribution polycarbonates at high conversion. This work presents a novel perspective for the preparation of tailorable multifunctional APCs.

Self-Amplified pH/ROS Dual-Responsive Co-Delivery Nano-System with Chemo-Photodynamic Combination Therapy in Hepatic Carcinoma Treatment.

Background: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy. Methods: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice. Results: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity. Conclusion: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.

Chemistry matters: A side-by-side comparison of two chemically distinct methacryloylated dECM bioresins for vat photopolymerization.

Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2-2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5-83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting.

Insight into the interaction of 5,6 epoxy-cholesterols with human serum albumin.

5,6-Epoxy-cholesterols has been recently revealed to control metabolic pathway in breast cancer, which makes investigating their binding interaction with human serum albumin (HSA) an attractive field of research. The main aim of this article is to examine the binding interaction of 5,6 α-epoxy-cholesterol (5,6 α EC) and 5,6 ß-epoxy-cholesterol (5,6 ß- EC) with HSA using different spectroscopic methods and molecular modeling. These compounds interact with HSA via hydrophobic interactions and hydrogen bonds with binding constants 6.3 × 105 M-1 for 5,6 α-epoxy-cholesterol and 6.9 × 105 M-1 for 5,6 ß-epoxy-cholesterol besides, the mechanism of the interaction can be attributed to static quenching. Circular dichroism data indicated that the α-helical content of HSA increased from 50.5 to 59.8 and 61.1 % after the addition of 5,6 α-ECs and 5,6 ß-EC, respectively, with a ratio of 1:2. Thermodynamic analysis revealed that binding between 5,6-epoxy-cholesterols and HSA is spontaneous and entropy-driven. The molecular docking and esterase-like activity experiments were performed to envision a link between the experimental and theoretical results. The optimal binding site of 5,6-epoxy-cholesterols with HSA was located in subdomain IIA. Moreover, theoretical calculations were performed using the B3LYP function with the 6-311++G (d,p) basis set, indicating the HOMO-LUMO energy gap of 7.874 eV for 5,6 α-epoxy-cholesterol and 7.873 eV for 5,6 ß-epoxy-cholesterol. The obtained findings are assumed to provide basic data for understanding the binding interactions of HSA with oxysterol compounds, which could help explore the pharmacokinetics and pharmacodynamics of oxysterol compounds.

Targeted drug-loaded peptides induce tumor cell apoptosis and immunomodulation to increase antitumor efficacy.

Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells via the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue. In an acidic environment, DT/Pep1 transformed from spherical nanoparticles to aggregates with a high aspect ratio, which successfully extended the retention of the drugs in the tumor cells and bolstered the anticancer effect. In both in vivo and in vitro experiments, DT/Pep1 effectively blocked the cell cycle and induced apoptosis. Importantly, the DT/Pep1 system efficiently suppressed tumor development in mice bearing 4T1 tumors while simultaneously promoting immune system activation. Thus, the results of this study provide a system for breast cancer therapy and offer a novel and promising platform for peptide nanocarrier-based drug delivery.

Enantioselective Total Synthesis of the Marine Macrolides Salarins A and C.

Here we report the first total synthesis of the marine macrolide salarin C, a potent anticancer agent, and demonstrate the biomimetic oxidation-Wasserman rearrangement to access salarin A. This synthesis relies on L-proline catalysis to install a chlorohydrin function that masks the sensitive C16-C17 epoxide and potentially mimics the biosynthesis of these compounds where a related chlorohydrin may yield both THF- and epoxide-containing salarins. Additional and key features of the synthesis include (i) macrocycle formation via ring-closing metathesis, (ii) macrocyclic substrate-controlled epoxidation of the C12-C13 allylic alcohol, and (iii) a late-stage Julia-Kocienski olefination to install the side chain. Importantly, this work provides a platform for the synthesis of other salarins and analogues of these potentially important anticancer natural products.

Epoxide Ring-Opening Reactions for Abundant Production of Mugineic Acids and Nicotianamine Probes.

A succinct synthetic approach to mugineic acids and 2'-hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring-opening reactions to form two C-N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'-hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'-hydroxy group. The dansyl-labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA-probe through these transporters.

Functional cellulose-derived epoxy cross-linked with BADGE resin to construct high-performance epoxy composites.

The development of equipped bio-based epoxy materials has been gaining much attention recently. Nevertheless, finding the balance between the structure and properties of materials remains a significant challenge. In this work, cellulose-based epoxy (PHPCEP) with "soft" and "hard" cooperative structures was designed and demonstrated to endow bisphenol A diglycidyl ether (BADGE) with excellent toughness, heat resistance, mechanical strength, glass transition temperature, thermal stability, and solvent resistance. When 5 wt% PHPCEP was incorporated into BADGE composites, the resulting materials exhibited the maximum flexural strength (121.9 MPa) and tensile strength (71.4 MPa), a high glass transition temperature (148.3 °C), and 10 wt% PHPCEP/BADGE demonstrated the highest impact strength (70.5 kJ/m2). These figures are 18.8 %, 16.1 %, 21.5 %, and 254.3 % higher than the corresponding values of neat BADGE. The results of dynamic mechanical properties and heat degradation of the cured specimens also suggest that PHPCEP/BADGE materials have superior stiffness and toughness than neat BADGE, which could be attributed to the strong interaction between PHPCEP and BADGE, delivering better thermal stability for the composites compared to the pristine resin. Considering the remarkable effect, this work provides an effective way of highly efficient utilization of abundant cellulose and a high-performance additive for composite materials.

Crosslinking of Epoxidized Natural Rubber with Borax for Self-Healing and Self-Repairing Properties: pH Dependence.

Epoxidized natural rubber (ENR) crosslinked using borax, which exhibits self-healing and self-repairing properties, is successfully developed. The crosslink formation of ENR by using borax under neutral and alkaline conditions is investigated. Fourier transform infrared spectroscopy (FTIR) shows that the borate-ester bond is formed in ENR prepared under both neutral and alkaline conditions, whereas boron nuclear magnetic resonance (11 B-NMR) results exhibit that the ENR prepared under alkaline conditions more actively forms crosslink networks with borax. Moreover, the crosslink density and gel content increase significantly with the presence of borax in alkaline conditions. The crosslink density and gel content of ENR with 10 phr borax are higher by 155% and 36%, respectively, than those of neat ENR. Furthermore, the formation of the crosslinking ENR by borax enhances self-healing and self-repairing properties. The healing efficiency significantly increases from 1.09% to 85.90%, when ENR is developed under alkaline conditions with 30 phr borax. These results represent the first successful demonstration of the efficient use of borax as a crosslinker in ENR, which exhibits its promising self-healing and self-repairing properties under atmospheric conditions without the need for external stimuli. The ENR prepared in this work holds great promise for various self-healing rubber applications.

Pharmacological activity and clinical progress of Triptolide and its derivatives LLDT-8, PG490-88Na, and Minnelide: a narrative review.

Triptolide, a compound isolated from a Chinese medicinal herb, has potent antitumor, immunosuppressive, and anti-inflammatory properties. Due to its interesting structural features and diverse pharmacological activities, it has attracted great interest by the Society of Organic Chemistry and Pharmaceutical Chemistry. However, its clinical potential is greatly hampered by limited aqueous solubility and oral bioavailability, and multi-organ toxicity. In recent years, various derivatives of Triptolide have made varying degrees of progress in the treatment of inflammatory diseases, autoimmune diseases, and cancer. The most researched and potentially clinically valuable of them were (5R)-5-hydroxytriptolide (LLDT-8), PG490-88Na (F6008), and Minnelide. In this review, we provide an overview of the advancements made in triptolide and several of its derivatives' biological activity, mechanisms of action, and clinical development. We also summarized some prospects for the future development of triptolide and its derivatives. It is hoped to contribute to a better understanding of the progress in this field, make constructive suggestions for further studies of Triptolide, and provide a theoretical reference for the rational development of new drugs.

Synthesis and Conformational Analysis of FR901464-Based RNA Splicing Modulators and Their Synergism in Drug-Resistant Cancers.

FR901464 is a cytotoxic natural product that binds splicing factor 3B subunit 1 (SF3B1) and PHD finger protein 5A (PHF5A), the components of the human spliceosome. The amide-containing tetrahydropyran ring binds SF3B1, and it remains unclear how the substituents on the ring contribute to the binding. Here, we synthesized meayamycin D, an analogue of FR901464, and three additional analogues to probe the conformation through methyl scanning. We discovered that the amide-containing tetrahydropyran ring assumes only one of the two possible chair conformations and that methylation of the nitrogen distorts the chair form, dramatically reducing cytotoxicity. Meayamycin D induced alternative splicing of MCL-1, showed strong synergism with venetoclax in drug-resistant lung cancer cells, and was cancer-specific over normal cells. Meayamycin D incorporates an alkyl ether and shows a long half-life in mouse plasma. The characteristics of meayamycin D may provide an approach to designing other bioactive L-shaped molecules.

Performance of cross-linked enzyme crystals of engineered halohydrin dehalogenase HheG in different chemical reactor systems.

Halohydrin dehalogenase HheG is an industrially interesting biocatalyst for the preparation of different ß-substituted alcohols starting from bulky internal epoxides. We previously demonstrated that the immobilization of different HheG variants in the form of cross-linked enzyme crystals (CLECs) yielded stable and reusable enzyme immobilizes with increased resistance regarding temperature, pH, and the presence of organic solvents. Now, to further establish their preparative applicability, HheG D114C CLECs cross-linked with bis-maleimidoethane have been successfully produced on a larger scale using a stirred crystallization approach, and their application in different chemical reactor types (stirred tank reactor, fluidized bed reactor, and packed bed reactor) was systematically studied and compared for the ring opening of cyclohexene oxide with azide. This revealed the highest obtained space-time yield of 23.9 kgproduct gCLEC -1 h-1 Lreactor volume -1 along with the highest achieved product enantiomeric excess [64%] for application in a packed-bed reactor. Additionally, lyophilization of those CLECs yielded a storage-stable HheG preparation that still retained 67% of initial activity (after lyophilization) after 6 months of storage at room temperature.

Mechanistic insight into homogeneous catalytic crosslinking behavior between cellulose and epoxide by explicit solvent models.

Inspired by recent advances on functional modification of cellulosic materials, the crosslinking behaviors of epoxide with cellulose under the catalysis of different homogeneous catalysts including H2O, Brønsted acid, Brønsted base, Lewis acid and neutral salt were systematically investigated using density functional theory (DFT) methods with hybrid micro-solvation-continuum approach. The results showed that catalytic activity, reaction mechanism and regioselectivity are determined by the combined effect of catalyst type, electronic effect and steric hindrance. All the homogeneous catalysts have catalytic activity for the crosslinking reaction, which decreases in the order of NaOH > HCl > NCl3 > MCl2 > CH3COOH > NaCl (N = Fe3+, Al3+; M = Zn2+, Ca2+). Upon the catalysis of NaOH, hydroxyl group of cellulose is firstly deprotonated to form a carbanion-like intermediate which will further attack the less sterically hindered C atom of epoxide showing excellent regioselectivity. Acidic catalysts readily cause epoxide protonated, which suffers from nucleophilic attack of cellulose and forms the carbocation-like intermediate. Brønsted acid exhibits poor regioselectivity, however, Lewis acid shows an interesting balance between catalytic activity and regioselectivity for the crosslinking reaction, which may be attributed to the unique catalysis and stabilization effects of its coordinated H2O on the transition state structure.

Systematic Development of Vanadium Catalysts for Sustainable Epoxidation of Small Alkenes and Allylic Alcohols.

The catalytic epoxidation of small alkenes and allylic alcohols includes a wide range of valuable chemical applications, with many works describing vanadium complexes as suitable catalysts towards sustainable process chemistry. But, given the complexity of these mechanisms, it is not always easy to sort out efficient examples for streamlining sustainable processes and tuning product optimization. In this review, we provide an update on major works of tunable vanadium-catalyzed epoxidations, with a focus on sustainable optimization routes. After presenting the current mechanistic view on vanadium catalysts for small alkenes and allylic alcohols' epoxidation, we argue the key challenges in green process development by highlighting the value of updated kinetic and mechanistic studies, along with essential computational studies.

The synthesis of multifunctional cellulose graft alternating copolymers of 3,4-dihydrocoumarin and epoxides in DBU/DMSO/CO2 solvent system.

Cellulose graft copolymers having well-defined structures could incorporate the characteristics of both the cellulose skeleton and side chains, providing a new method for the preparation functionalised cellulose derivatives. Herein, a series of multifunctional cellulose grafted, alternating 3,4-dihydrocoumarin (DHC) and epoxide (EPO) copolymers (cell-g-P(DHC-alt-EPO)) were prepared in a metal-free DBU/DMSO/CO2 solvent system without adding additional catalyst. Four examples of cell-g-P(DHC-alt-EPO) with tunable thermal and optical properties were synthesized by copolymerization of DHC with styrene oxide (SO), propylene oxide (PO), cyclohexene oxide (CHO) or furfuryl glycidyl ether (FGE) onto cellulose. The nonconjugated cell-g-P(DHC-alt-EPO) showed UV absorption properties with the maximum absorption peak at 282 nm and 295 nm and photoluminescence performance. A clustering-triggered emission mechanism was confirmed and consistent with DFT theoretical calculations. In DMSO solution, the copolymer (DHCSO5) with DP of 11.64 showed ACQ behaviour as the concentration increased. In addition, DHCSO5 had good antioxidant capacity with an instantaneous radical scavenging activity of 2,2-diphenyl-1-picrylhydrazine (DPPH) up to 65 % at a concentration of 40 mg/ ml and increased to 100 % after 30 min. Thus, the multifunctional cell-g-P(DHC-alt-EPO) materials had a variety of potential applications in the fields of fluorescent printing, bio-imaging, UV- shielding and antioxidants.

Isotope Labeling Mass Spectrometry to Quantify Endogenous and Exogenous DNA Adducts and Metabolites of 1,3-Butadiene In Vivo.

Human exposure to known carcinogen 1,3-butadiene (BD) is common due to its high concentrations in automobile exhaust, cigarette smoke, and forest fires, as well as its widespread use in the polymer industry. The adverse health effects of BD are mediated by epoxide metabolites such as 3,4-epoxy-1-butene (EB), which reacts with DNA to form 1-hydroxyl-3-buten-1-yl adducts on DNA nucleobases. EB-derived mercapturic acids (1- and 2-(N-acetyl-l-cysteine-S-yl)-1-hydroxybut-3-ene (MHBMA) and N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA)) and urinary N7-(1-hydroxyl-3-buten-1-yl) guanine DNA adducts (EB-GII) have been used as biomarkers of BD exposure and cancer risk in smokers and occupationally exposed workers. However, low but significant levels of MHBMA, DHBMA, and EB-GII have been reported in unexposed cultured cells, animals, and humans, suggesting that these metabolites and adducts may form endogenously and complicate risk assessment of butadiene exposure. In the present work, stable isotope labeling in combination with high-resolution mass spectrometry was employed to accurately quantify endogenous and exogenous butadiene metabolites and DNA adducts in vivo. Laboratory rats were exposed to 0.3, 0.5, or 3 ppm of BD-d6 by inhalation, and the amounts of endogenous (d0) and exogenous (d6) DNA adducts and metabolites were quantified in tissues and urine by isotope dilution capillary liquid chromatography/high resolution electrospray ionization tandem mass spectrometry (capLC-ESI-HRMS/MS). Our results reveal that EB-GII adducts and MHBMA originate exclusively from exogenous exposure to BD, while substantial amounts of DHBMA are formed endogenously. Urinary EB-GII concentrations were associated with genomic EB-GII levels in tissues of the same animals. Our findings confirm that EB-GII and MHBMA are specific biomarkers of exposure to BD, while endogenous DHBMA predominates at sub-ppm exposures to BD.

Diamine-modified porous indium frameworks with crystalline porous materials (CPM)-5 structure for carbon dioxide fixation under co-catalyst and solvent free conditions.

In the present work, functional diamine groups into indium frameworks to synthesize cyclic carbonates from CO2 and epoxides with efficient catalytic activity in the absence of co-catalyst and solvent are reported for the first time. Crystalline porous materials (CPM)-5 modified with 1,2-phenylene diamine and ethylene diamine (CPM-5-PhDA and CPM-5-EDA), were prepared using a post-synthetic modification (PSM) method. The properties of the modified CPM-5 were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), N2-adsorption, scanning electron microscopy (SEM), CO2 adsorption, and temperature programmed desorption TPD methods. The presence of diamine groups as basic sites and indium Lewis acid sites in the framework structure were desirable for high catalytic activity. For a given catalyst weight, CPM-5-PhDA was the best candidate to appear with great catalytic activity and selectivity for the cycloaddition reaction at 100°C and 1 MPa CO2 under co-catalyst and solvent free conditions. CPM-5-PhDA also was found to afford large and bulky epoxides. The catalyst can be easily separated and reused five times without any decline in activity.

Cobalt-Catalyzed Stereospecific C-N/C-O Bond Formation of Oxiranes with Diaziridines.

Co-catalyzed stereospecific C-N and C-O bond formation of oxiranes with diaziridines has been accomplished to furnish tetrahydro-[1,3,4]-oxadiazines at room temperature. Optically active oxiranes can be coupled with high optical purities (>96% ee). Stereoselectivity, functional group tolerance, mechanistic studies using DFT, and natural product modification are the important practical features.

Biobased epoxidized natural rubber/sodium carboxymethyl cellulose composites with enhanced strength and healing ability.

Conventional vulcanized rubbers cause a non-negligible waste of resources due to the formation of 3D irreversible covalently cross-linked networks. The introduction of reversible covalent bonds, such as reversible disulfide bonds, into the rubber network, is an available solution to the above problem. However, the mechanical properties of rubber with only reversible disulfide bonds cannot meet most practical applications. In this paper, a strengthened bio-based epoxidized natural rubber (ENR) composite reinforced by sodium carboxymethyl cellulose (SCMC) was prepared. SCMC forms a mass of hydrogen bonds between its hydroxyl groups and the hydrophilic groups of ENR chain, which gives the ENR/2,2'-Dithiodibenzoic acid (DTSA)/SCMC composites an enhanced mechanical performance. With 20 phr SCMC, the tensile strength of the composite increases from 3.0 to 10.4 MPa, which is almost 3.5 times that of the ENR/DTSA composite without SCMC. Simultaneously, DTSA covalently cross-linked ENR with the introduction of reversible disulfide bonds, which enables the cross-linked network to rearrange its topology at low temperatures and thus endows the ENR/DTSA/SCMC composites with healing properties. The ENR/DTSA/SCMC-10 composite has a considerable healing efficiency of about 96 % after healing at 80 °C for 12 h.