thiol-Michael Addition Research Articles

Synthesis of linear and crosslinked isosorbide-containing poly(β-thioether ester) via amine-catalyzed thiol-Michael addition

In this work, the amine-catalyzed thiol-Michael reaction of isosorbide or isomannide-derived dithiols as Michael-donors, with some diacrylates and dimethacrylates as Michael-acceptors, is reported. In a first part, different amines (1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), dimethylaminopyridine (DMAP), Amberlyst® A-21 and hexylamine (HA)) were tested as catalysts for reactions involving diacrylates and dimethacrylates in acetonitrile, respectively. Molecular weight taken as the relevant criterion, DBU and DMAP were found to be equally efficient for polymerization with acrylates while DBU was the most efficient one with methacrylates. A library of polymers differing from the structure of the used diacrylate (some of them derived from isosorbide or isomannide) or dimethacrylate was prepared, with fair molecular weights and Tg varying from –22 to +32 °C. Then oligomers with controlled molecular weight and good end group fidelity were prepared, and were further used in a two-stage crosslinking reaction to prepare soft and elastic biobased crosslinked polymers via thiol-Michael addition.

Injectable self-healing alginate/PEG hydrogels cross-linked via thiol-Michael addition bonds for hemostasis and wound healing

In this study, an alginate/PEG hydrogel was developed via a thiol-Michael addition reaction between oxidized quinone of catechols on dopamine-grafted sodium alginate (SA-DA) and sulfhydryl groups of 4-arm polyethylene glycol tetra-thiol (4-arm PEG-SH) under mildly basic conditions. Through the formation of thiol-terminated catechol groups, the accompanying oxidized catechols are reduced, significantly strengthening the internal network structure of the hydrogel and improving tissue adhesion. Meanwhile, the hydrogels have excellent self-healing properties due to the dynamic non-covalent bonds between the groups. Adjustment of hydrogel properties by varying the mass ratio of two hydrogel precursors. Due to the high content of thiol-terminated catechol groups, the Gel 3 exhibited good tissue adhesion, rapid self-healing ability, and other multifunctions beneficial to wound healing, including killing of E. coli and S. aureus, rapid hemostasis and promoting migration of L929 cells. The full-thickness skin wound model shows that the hydrogel dressing significantly accelerated wound contraction, with increased granulation tissue thickness, collagen disposition, and enhanced vascularization, thus promoting wound healing. Therefore, the thiol-Michael addition reaction is an effective method for creating multifunctional hydrogels, and the injectable self-healing alginate/PEG hydrogels prepared in this way could be used in the biomedical area as wound healing dressing materials.

Non‐Isocyanate Synthesis of Covalent Adaptable Networks Based on Dynamic Hindered Urea Bonds: Sequential Polymerization and Chemical Recycling

AbstractThe development of environmentally sustainable processes for polymer recycling is of paramount importance in the polymer industry. In particular, the implementation of chemical recycling for thermoset polymers via covalent adaptable networks (CANs), particularly those based on the dynamic hindered urea bond (HUB), has garnered intensive attention from both the academic and industrial sectors. This interest stems from its straightforward chemical structure and reaction mechanism, which are well‐suited for commercial polyurethane and polyurea applications. However, a substantial drawback of these CANs is the requisite use of toxic isocyanate curing agents for their synthesis. Herein, we propose a new HUB synthesis pathway involving thiazolidin‐2‐one and a hindered amine. This ring‐opening reaction facilitates the isocyanate‐free formation of a HUB and enables sequential reactions with acrylate and epoxide monomers via thiol–Michael and thiol–epoxy click chemistry. The CANs synthesized using this methodology exhibit superior reprocessability, chemical recyclability, and reutilizability, facilitated by specific catalytic and solvent conditions, through the reversible HUB, thiol–Michael addition, and transesterification processes.

Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications.

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. Even after surgery and chemoradiotherapy, residual GBM cells can infiltrate the healthy brain parenchyma to form secondary tumors. To mitigate GBM recurrence, we recently developed an injectable hydrogel that can be crosslinked in the resection cavity to attract, collect, and ablate residual GBM cells. We previously optimized a thiol-Michael addition hydrogel for physical, chemical, and biological compatibility with the GBM microenvironment and demonstrated CXCL12-mediated chemotaxis can attract and entrap GBM cells into this hydrogel. In this study, we synthesize hydrogels under conditions mimicking GBM resection cavities and assess feasibility of histotripsy to ablate hydrogel-encapsulated cells. The results showed the hydrogel synthesis was bio-orthogonal, not shear-thinning, and can be scaled up for injection into GBM resection mimics in vitro. Experiments also demonstrated ultrasound imaging can distinguish the synthetic hydrogel from healthy porcine brain tissue. Finally, a 500kHz transducer applied focused ultrasound treatment to the synthetic hydrogels, with results demonstrating precise histotripsy bubble clouds could be sustained in order to uniformly ablate red blood cells encapsulated by the hydrogel for homogeneous, mechanical fractionation of the entrapped cells. Overall, this hydrogel is a promising platform for biomaterials-based GBM treatment.

Light Switchable Bioorthogonal Reaction Manifold for Modulation of Hydrogel Properties.

Chemical reaction systems that can occur via multiple pathways in a controllable fashion are highly attractive for advanced materials applications and biological research. In this report, we introduce a bioorthogonal reaction manifold based on a chalcone pyrene (CPyr) moiety that can undergo either red-shifted photoreversible [2 + 2] cycloaddition or thiol-Michael addition click reaction. By coupling the CPyr to a water-soluble poly(ethylene glycol) end group, we demonstrate the efficient polymer dimerization and cleavage by blue light (λ = 450 nm) and UV light (λ = 340 nm), respectively. In the absence of light, CPyr rapidly reacts with thiols in aqueous environments, enabling fast and efficient polymer end-group functionalization. The chemical reaction manifold was further employed in polymer cross-linking for the preparation of hydrogels whose stiffness and morphology can be modulated by different photonic fields or the addition of a thiol cross-linker. The photoreversible cycloaddition and thiol-Michael addition click reaction can be used in conjunction for spatial and temporal conjugation of a streptavidin protein. Both cross-linking conditions are nontoxic to various cell lines, highlighting their potential in biomaterials applications.

Non-Isocyanate Synthesis of Covalent Adaptable Networks Based on Dynamic Hindered Urea Bonds: Sequential Polymerization and Chemical Recycling.

The development of environmentally sustainable processes for polymer recycling is of paramount importance in the polymer industry. In particular, the implementation of chemical recycling for thermoset polymers via covalent adaptable networks (CANs), particularly those based on the dynamic hindered urea bond (HUB), has garnered intensive attention from both the academic and industrial sectors. This interest stems from its straightforward chemical structure and reaction mechanism, which are well-suited for commercial polyurethane and polyurea applications. However, a substantial drawback of these CANs is the requisite use of toxic isocyanate curing agents for their synthesis. Herein, we propose a new HUB synthesis pathway involving thiazolidin-2-one and a hindered amine. This ring-opening reaction facilitates the isocyanate-free formation of a HUB and enables sequential reactions with acrylate and epoxide monomers via thiol-Michael and thiol-epoxy click chemistry. The CANs synthesized using this methodology exhibit superior reprocessability, chemical recyclability, and reutilizability, facilitated by specific catalytic and solvent conditions, through the reversible HUB, thiol-Michael addition, and transesterification processes.

A novel epoxy-based self-healing robust superhydrophobic coatings for oil/water separation

Low durability greatly limits the practical application of superhydrophobic coating. In this study, we report a method of employing low surface energy materials and chemically reactive epoxy groups that possess strong adhesion on substrates in one system to solve the durability issue. A branched epoxy with dangling long polydimethylsiloxane (PDMS) tail was first synthesized through a thiol-Michael addition reaction. After curing, this coating exhibited superhydrophobicity with the contact angles (CAs) of 162.8 ± 1.0° and excellent durability towards strong acid (pH = 1.0), organic solvents as well as thermal treatment (150 °C, 24 h). Notably, the CAs of this coating could maintain above 150° after 80 times of sandpaper abrasions, 100 times of tape-peeling, and 240 min of ultrasonic treatment, respectively. More importantly, the coating could spontaneously revert to a superhydrophobic state at room temperature after being plasma-treated to a superhydrophilic state. The coating fabric was utilized to separate the mixture of oil/water and the efficiencies for blend oil, corn oil, and soybean oil were found to be 97.7 ± 0.4 %, 98.2 ± 0.5 %, and 98.7 ± 0.3 %, respectively. This work provides a novel strategy to create a fluorine-free, self-healing, and robust superhydrophobic coating.

Chitosan films synthesized via thiol-ene click chemistry: Toward safe and versatile platforms for packaging, cosmetics and biomedical applications

The first synthesis of chitosan-based films using bio-based reticulating agents via Thiol-Michael addition click reaction was described, along with their successful application in packaging, cosmetics, and biomedical fields. The impact of chitosan (CS) concentration and the type of synthesized bio-sourced biacids (GD) and triacids (GT and TT) on the physicochemical properties of these films were assessed. Films prepared with dibasic and tribasic acids (4%-CS) demonstrated superior mechanical properties and lower solubility compared to those containing 2% CS. The incorporation of the bio-sourced GD, GT, and TT acids led to a reduction of 53%, 60% and 60.4%, respectively, in the water vapor permeability (WVP) of 4% CS-based films compared to the control film. Remarkably, CS-TT-4% films exhibited the highest mechanical strength (TS), elongation at break (%E), elasticity, water vapor, and light barrier properties. Cytotoxicity tests performed on the NIH 3T3 fibroblast cell line showed that CS-GD-4% films exhibited the highest compatibility. The efficiency of these films as drug carriers was tested with challenging anticancer and cosmetic molecules, particularly etoposide (ETP) caffeine (Caf), showing very high drug loading with a progressive release of less than 20% after 72h of incubation. Moreover, ex-vivo permeation studies in rat skin revealed that the percutaneous absorption of Caf is significantly increased by a factor of 5.5 compared to that of CS-GD-4%-Caf films with no significant histological alterations of skin layers. Altogether, this work evidences the most suitable casting solvent for developing safe chitosan films, promising their potential applications in the cosmetic and biomedical fields.

Smart responsive in situ hydrogel systems applied in bone tissue engineering.

The repair of irregular bone tissue suffers severe clinical problems due to the scarcity of an appropriate therapeutic carrier that can match dynamic and complex bone damage. Fortunately, stimuli-responsive in situ hydrogel systems that are triggered by a special microenvironment could be an ideal method of regenerating bone tissue because of the injectability, in situ gelatin, and spatiotemporally tunable drug release. Herein, we introduce the two main stimulus-response approaches, exogenous and endogenous, to forming in situ hydrogels in bone tissue engineering. First, we summarize specific and distinct responses to an extensive range of external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) to form in situ hydrogels created from biocompatible materials modified by various functional groups or hybrid functional nanoparticles. Furthermore, "smart" hydrogels, which respond to endogenous physiological or environmental stimuli (e.g., temperature, pH, enzyme, etc.), can achieve in situ gelation by one injection in vivo without additional intervention. Moreover, the mild chemistry response-mediated in situ hydrogel systems also offer fascinating prospects in bone tissue engineering, such as a Diels-Alder, Michael addition, thiol-Michael addition, and Schiff reactions, etc. The recent developments and challenges of various smart in situ hydrogels and their application to drug administration and bone tissue engineering are discussed in this review. It is anticipated that advanced strategies and innovative ideas of in situ hydrogels will be exploited in the clinical field and increase the quality of life for patients with bone damage.

Highly water-soluble and migration stable photoinitiators from meso-2,3-dimercaptosuccinic acid

A facile route to prepare highly water-soluble and migration stable Type I and Type II photoinitiators is reported. The mono- or doubly 2-hydroxy-4′-(2-hydroxyethoxy)-2 methylpropiophenone (I2959), 1-hydroxycyclohexyl phenyl ketone (I184) and benzophenone (BP) functionalized meso-2,3-dimercaptosuccinic acid (DMSA) salts with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or sodium counterion (DMSA-I2959-DBU, DMSA-I184-Na, DMSA-BP-Na, DMSA-BP-DBU) are synthesized in one-pot thiol-Michael addition reaction. Although DMSA-I2959-DBU and DMSA-I184-Na have higher water solubility (e.g. 16 times higher than that of I2959 for the first one) than I2959 and I184, BP functionalized PIs are not stable in water. The synthesized photoinitiators have similar or higher λmax compared to the commercial ones they are synthesized from. The decomposition mechanism and the radical generations are investigated by steady state photolysis and electron spin resonance (ESR). They show reasonable photoinitiating reactivity towards (meth)acrylic double bonds except the I184-based one. The higher migration stability of photoinitiators (DMSA-I2959-DBU has ∼4 times higher than that of I2959), is due to their and unreactive photodecomposition byproducts’ high molecular weight.

Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers.

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

The Michael addition of thiols to 13-oxo-octadecadienoate (13-oxo-ODE) with implications for LC-MS analysis of glutathione conjugation

Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products exhibit a conjugated enone UV chromophore, a result that conflicts with the literature and relevant to mass spectral interpretation of 1,4 versus 1,6 thiol adduction. Aided by development of an HPLC solvent system that separates the GSH diastereomers and thus avoids overlap of signals in proton NMR experiments, we established the two major conjugates are formed by 1,6 addition of GSH at the 9-carbon of 13-oxo-ODE with the remaining double bond α to the thiol in the 10,11 position. N-acetyl cysteine reacts similarly, while β-mercaptoethanol gives equal amounts of 1,4 and 1,6 addition products. Equine glutathione transferase catalyzed 1,6 addition of GSH to the two major diastereomers in 44:56 proportions. LC-MS in positive ion mode gives a product ion interpreted before as evidence of 1,4-thiol adduction, whereas here we find this ion using the authentic 1,6 adduct. LC-MS with negative ion APCI gave a fragment selective for 1,4 adduction. These results clarify the structures of thiol conjugates of a prototypical unsaturated keto fatty acid and have relevance to the application of LC-MS for the structural analysis of keto-fatty acid glutathione conjugation.

In situ crosslinkable multi-functional and cell-responsive alginate 3D matrix via thiol-maleimide click chemistry

In vivo, cells interact with the extracellular matrix (ECM), which provides a multitude of biophysical and biochemical signals that modulate cellular behavior. Inspired by this, we explored a new methodology to develop a more physiomimetic polysaccharide-based matrix for 3D cell culture. Maleimide-modified alginate (AlgM) derivatives were successfully synthesized using DMTMM to activate carboxylic groups. Thiol-terminated cell-adhesion peptides were tethered to the hydrogel network to promote integrin binding. Rapid and efficient in situ hydrogel formation was promoted by thiol-Michael addition “click” chemistry via maleimide reaction with thiol-flanked protease-sensitive peptides. Alginate derivatives were further ionically crosslinked by divalent ions present in the medium, which led to greater stability and allowed longer cell culture periods. By tailoring alginate's biofunctionality we improved cell-cell and cell-matrix interactions, providing an ECM-like 3D microenvironment. We were able to systematically and independently vary biochemical and biophysical parameters to elicit specific cell responses, creating custom-made 3D matrices. DMTMM-mediated maleimide incorporation is a promising approach to synthesizing AlgM derivatives that can be leveraged to produce ECM-like matrices for a broad range of applications, from in vitro tissue modeling to tissue regeneration.

Acidic Derivatization of Thiols Using Diethyl 2-Methylenemalonate: Thiol-Michael Addition Click Reaction for Simultaneous Analysis of Cysteine and Cystine in Culture Media Using LC-MS/MS.

Cysteine (Cys) and its oxidized form, cystine (Cys2), play crucial roles in biological systems and have considerable applications in cell culture. However, Cys in cell culture media is easily oxidized to Cys2, leading to solubility issues. Traditional analytical methods struggle to maintain the oxidation states of Cys and Cys2 during analysis, posing a significant challenge to accurately measuring and controlling these compounds. To effectively control the Cys and Cys2 levels, a rapid and accurate analytical method is required. Here, we screened derivatizing reagents that can react with Cys even under acidic conditions to realize a novel analytical method for simultaneously determining Cys and Cys2 levels. Diethyl 2-methylenemalonate (EMM) was found to possess the desired traits. EMM, characterized by its dual electron-withdrawing attributes, allowed for a rapid reaction with Cys under acidic conditions, preserving intact information for understanding the functions of target compounds. Combined with LC-MS/MS and an internal standard, this method provided high analytical accuracy in a short analytical time of 9 min. Using the developed method, the rapid oxidation of Cys in cell culture media was observed with the headspace of the storage container considerably influencing Cys oxidation and Cys2 precipitation rates. The developed method enabled the direct and simplified analysis of Cys behavior in practical media samples and could be used in formulating new media compositions, ensuring quality assurance, and real-time analysis of Cys and Cys2 in cell culture supernatants. This novel approach holds the potential to further enhance the media performance by enabling the timely optimal addition of Cys.

A Study on Thiol-Michael Addition to Semi-Synthetic Elastin-Hyaluronan Material for Electrospun Scaffolds.

Thiol-Michael addition is a chemical reaction extensively used for conjugating peptides to polysaccharides with applications as biomaterials. In the present study, for designing a bioactive element in electrospun scaffolds as wound dressing material, a chemical strategy for the semi-synthesis of a hyaluronan-elastin conjugate containing an amide linker (ELAHA) was developed in the presence of tris(2-carboxyethyl)phosphine hydrochloride (TCEP ⋅ HCl). The bioconjugate was electrospun with poly-D,L-lactide (PDLLA), obtaining scaffolds with appealing characteristics in terms of morphology and cell viability of dermal fibroblast cells. For comprehending the factors influencing the efficiency of the bioconjugation reaction, thiolated amino acids were also investigated as nucleophiles toward hyaluronan decorated with Michael acceptors in the presence of TCEP ⋅ HCl through the evaluation of byproducts formation.

Metal-free thiol-Michael addition for hydrogen bond-rich poly(dimethyl siloxane) networks with improved electromechanical properties and self-healing capabilities

Novel use of thiol-Michael addition enables metal-free cross-linking of PDMS, enhancing self-healing and dielectric properties.

3D printing of reactive macroporous polymers via thiol-ene chemistry and polymerization-induced phase separation.

Using thiol-ene chemistry, polymerization-induced phase separation, and DLP 3D printing, we present a method for manufacturing reactive macroporous 3D structures. This approach enables the fabrication of structures with tunable physicochemical properties and compressibility. Moreover, it facilitates post-functionalization through thiol-Michael addition reactions, thereby expanding performance and application potential.

A divergent one-pot thiol-Michael strategy to create β-thiophene-fused porphyrins.

A divergent one-pot domino strategy for the synthesis of nickel(II) and copper(II) β-thiophene-fused 5,10,15,20-tetraarylporphyrins was developed through a thiol-Michael addition of thioglycolic/thiolactic acid to the corresponding 2-iminoporphyrins, formed in situ after the reaction of nickel(II) and copper(II) 2-formyl-5,10,15,20-tetraarylporphyrins with sterically hindered tert-butylamine in 1,2-dichloroethane at 80 °C. Interestingly, the reaction of 2-formylporphyrins with comparatively less sterically hindered primary amines and thioglycolic acid afforded a mixture of β-substituted porphyrinic thiazolidinones and β-thiophene-fused porphyrins. A similar one-pot thiol-Michael protocol was applied to construct a novel free-base thieno[2,3-b]-meso-tetrakis(4-methoxyphenyl)porphyrin, which underwent zinc insertion by using zinc acetate in a CHCl3-MeOH mixture and afforded zinc(II) β-thiophene-fused meso-tetrakis(4-methoxyphenyl)porphyrin in an appreciable isolated yield. On photophysical evaluation, these new porphyrins displayed a modest bathochromically shifted electronic absorption in contrast to meso-tetraarylporphyrin building blocks.

ROS-Responsive 4D Printable Acrylic Thioether-Based Hydrogels for Smart Drug Release.

Reactive oxygen species (ROS) play a key role in several biological functions like regulating cell survival and signaling; however, their effect can range from beneficial to nondesirable oxidative stress when they are overproduced causing inflammation or cancer diseases. Thus, the design of tailor-made ROS-responsive polymers offers the possibility of engineering hydrogels for target therapies. In this work, we developed thioether-based ROS-responsive difunctional monomers from ethylene glycol/thioether acrylate (EGnSA) with different lengths of the EGn chain (n = 1, 2, 3) by the thiol-Michael addition click reaction. The presence of acrylate groups allowed their photopolymerization by UV light, while the thioether groups conferred ROS-responsive properties. As a result, smart PEGnSA hydrogels were obtained, which could be processed by four-dimensional (4D) printing. The mechanical properties of the hydrogels were determined by rheology, pointing out a decrease of the elastic modulus (G') with the length of the EG segment. To enhance the stability of the hydrogels after swelling, the EGnSA monomers were copolymerized with a polar monomer, 2-hydroxyethyl acrylate (HEA), leading to P[(EGnSA)x-co-HEAy] with improved compatibility in aqueous media, making it a less brittle material. Swelling properties of the hydrogels increased in the presence of hydrogen peroxide, a kind of ROS, reaching values of ≈130% for P[(EG3SA)7-co-HEA93] which confirms the stimuli-responsive properties. Then, the P[(EG3SA)x-co-HEAy] hydrogels were employed as matrixes for the encapsulation of a chemotherapeutic drug, 5-fluorouracil (5FU), which showed sustained release over time modulated by the presence of H2O2. Finally, the effect of the 5-FU release from P[(EG3SA)x-co-HEAy] hydrogels was tested in vitro with melanoma cancer cells B16F10, pointing out B16F10 growth inhibition values in the range of 40-60% modulated by the EG3SA percentage and the presence or absence of ROS agents, thus confirming their excellent ROS-responsive properties for the treatment of localized pathologies.

Programmable liquid crystal elastomers with dynamic covalent siloxane bonds based on a dual self-catalytic strategy

The exchange reaction of preparing the siloxane-based liquid crystal elastomers (Si-LCEs) always require the acid or base catalysts, which will increase the complexity of the operation and reduces the stability of the Si-LCE materials. In this paper, a novel and simple dual self-catalytic strategy for producing Si-LCEs with dynamic covalent siloxane bonds was proposed. A readily available compound-1,3-bis (aminopropyl) tetramethyldisiloxane (BATS) acts as chain extender and crosslinker for elastomers and provides dynamic covalent bonds (DCBs) as well. More importantly, amino groups of BATS play the role of dual self-catalyst, not only accelerating the thiol Michael addition reaction and aza Michael addition reaction simultaneously during producing Si-LCEs, but also promoting dynamic covalent siloxane bonds exchange reaction at an elevated temperature after the formation of the cross-linked network. With this ingenious design, the obtained fully cured polydomain Si-LCEs possess excellent self-healing and processing abilities enabled by DCBs and outstanding mechanical properties facilitated by hydrogen bond, which can be easily aligned, programmed and recycled. By exploiting these dynamic features, a series of multi-functional soft actuators were realized by simple welding, showing a local fast response and precise control by light and heat. Furthermore, soft robots fabricated with a bilayer structure of Si-LCEs can perform crawling and coiling actuation controlled by near-infrared (NIR) light facilely. These results manifest that the self-catalytic dynamic covalent siloxane bonds strategy is a facile and effective approach for preparing Si-LCEs and provides a new solution for the exploitation of multi-functional liquid crystal elastomers with fast response to various stimulus.