Macromonomer containing light-controlled broken bond unit and synthesis method and application thereof

Abstract

The invention discloses a macromonomer containing a light-controlled broken bond unit as well as a synthesis method and application of the macromonomer, and belongs to the technical field of macromolecular functional materials. The macromonomer is formed by covalently connecting a macromolecular chain, a photoresponse breaking functional group and a molecular fragment containing a catechol structure through a chemical bond; the synthesis method specifically comprises the following steps: (1) synthesizing an intermediate A containing a photoresponse fracture functional group; (2) carrying out a coupling reaction with a molecular fragment containing a catechol structure; and (3) carrying out a coupling reaction with a polymer chain containing an active functional group in a solvent under the catalytic action of a condensing agent to obtain the product. The macromonomer disclosed by the invention shows remarkable technical advantages in the aspects of structure function integration, response performance regulation, biological interface adhesion, application diversity and the like, and has a wide application prospect and popularization value; the preparation method is especially suitable for the frontier crossing fields of intelligent hydrogel materials, biological adhesives, tissue engineering scaffolds, flexible implantable electronic equipment and the like.

Description

Technical Field

[0001] This invention relates to the field of polymer functional materials technology, and more specifically to a macromolecular monomer containing a photo-controlled bond-breaking unit, its synthesis method, and its application. Background Technology

[0002] With the rapid development of biomedical materials and flexible electronic devices, functional hydrogels have become a research hotspot in fields such as tissue engineering, controlled drug release, and flexible encapsulation due to their excellent flexibility, tissue compatibility, and designability. In these applications, hydrogels not only need to possess good mechanical and biological properties, but also often require exogenous controllable responsiveness to adapt to complex and ever-changing application environments.

[0003] In recent years, photoresponsive materials have been widely used in the construction of smart hydrogels due to their high spatial and temporal resolution, non-contact stimulation, and tunable degradation behavior. Among them, photosensitive structures based on the breaking of chemical bonds induced by ultraviolet light irradiation, such as o-nitrobenzyl ester, coumarin, and O-acyl oxime, have been successfully introduced into polymer systems to achieve phototriggered degradation or structural changes.

[0004] Patent CN 114262408 A discloses a photoresponsive degradable hydrogel wound dressing, its synthesis method, and its application. This hydrogel wound dressing comprises a flexible network and a rigid network. The flexible network includes a polymer containing multiple carboxyl groups and metal ions, while the rigid network includes a polyacrylamide network containing 1-(2-nitro)phenylethyl acrylate crosslinking groups. The introduction of 1-(2-nitro)phenylethyl acrylate as a crosslinking group endows the hydrogel wound dressing with rapid degradation behavior in response to ultraviolet light, thereby achieving rapid degradation during secondary dressing changes. However, the lack of a systematic structural design makes it difficult to achieve the dual functions of "photoresponsiveness + adhesion."

[0005] Patent CN 108794737 A discloses a UV-responsive end-capped modified polyethylene glycol crosslinking agent and its preparation method, as well as a hydrogel dressing containing the crosslinking agent and its preparation method. This addresses the technical problem of existing hydrogel dressings causing wound pain and secondary trauma during wound re-treatment and removal. The hydrogel dressing containing the UV-responsive end-capped modified polyethylene glycol crosslinking agent is formed using an injectable in-situ gelation method. This gelation method has good adaptability to wound shape and provides better adhesion compared to pre-gelled block dressings, without requiring auxiliary fixation materials. When further wound treatment is needed, the hydrogel dressing of this invention can be applied at a rate of 10 mw / cm. 2The gel is softened and degraded by selectively irradiating it with 365nm ultraviolet light. However, these photoresponsive systems are mostly based on a single-structure degradation mechanism and lack broad-spectrum adhesion in their molecular design, making it difficult to work synergistically with different substrate surfaces.

[0006] On the other hand, natural molecules with catechol structures (such as dopamine and catechins) exhibit excellent adhesion to various substrates in humid environments, showing unique advantages in the adhesive design of hydrogels. Although some studies have attempted to incorporate catechol molecules into polymer systems, the synergistic construction strategy between them and photoresponsive units is still immature, creating bottlenecks in multifunctional integrated design. For example, patent CN 106693039 A discloses a method for synthesizing a medical hydrogel with good bioadhesion. The raw materials for preparing this hydrogel include end-group modified four-arm polyethylene glycol dopamine and four-arm polyethylene glycol phenylboronic acid. The two components are physically mixed using a mixing tool and then covalently cross-linked to form a hydrogel. The advantage of this invention is that the presence of dopamine groups endows the hydrogel with strong bioadhesion and self-healing properties. However, its bioadhesion performance is difficult to control, especially in applications requiring controllable deadhesion (such as non-invasive removal of implants).

[0007] Therefore, how to incorporate the catechol structure into the adhesive design of hydrogels is a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0008] In view of this, the purpose of this invention is to provide a macromolecular monomer containing a photosensitive bond-breaking unit, its synthesis method and application, so as to solve the problems of single structure and function, uncontrollable adhesion and limited degradability of photosensitive polymer materials in the prior art.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] A macromonomer containing a photo-controlled bond-breaking unit is composed of a polymer chain, a photoresponsive cleavage functional group (at least one), and a molecular segment containing a catechol structure (at least one) covalently linked by chemical bonds.

[0011] Furthermore, the aforementioned polymer chain is at least one of hydrophilic polymers, amphiphilic polymers, and hydrophobic polymers.

[0012] Furthermore, the aforementioned hydrophilic polymer is at least one of polyethylene glycol (PEG), polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC), polyacrylamide (PAM), polyethyleneimine (PEI), gelatin, chitosan, and hyaluronic acid;

[0013] The amphiphilic polymer is at least one of the following: polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) block copolymer (Pluronic), poly(polyethylene glycol methacrylate) (POEGMA), polycaprolactone-polyethylene glycol (PCL-PEG) block copolymer, and poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer;

[0014] The hydrophobic polymer is at least one of polylactic acid (PLA), polycaprolactone (PCL), polycarbonate, and aliphatic polyester.

[0015] Furthermore, the aforementioned polymer chain is at least one of linear polyethylene glycol, three-arm polyethylene glycol, four-arm polyethylene glycol, and eight-arm polyethylene glycol, with a number average molecular weight of 1,000-50,000 Daltons, preferably 6,000-20,000 Daltons.

[0016] The further beneficial effect of the above-mentioned method is that the polymer chain selected in this invention is the middle part of the macromolecular monomer, which can serve as a flexible skeleton to connect functional units.

[0017] Furthermore, the aforementioned photoresponsive cleavage functional group is at least one of the photosensitive structures such as o-nitrobenzyl ester, coumarin, O-acyl oxime, anthracene, thymine, and O-acyl oxime, and the specific structure is adjusted according to the target application.

[0018] The further beneficial effect of the above-mentioned method is that the photoresponsive cleavage functional group selected in this invention can undergo covalent bond cleavage under ultraviolet light irradiation, thereby endowing macromolecular monomers with controllable photodegradation ability.

[0019] Furthermore, the aforementioned molecular fragments containing catechin structures are at least one of dopamine (3,4-dihydroxyphenylethylamine), catechin, epicatechin, protocatechuic acid, catechin amines, and tannic acid.

[0020] The further beneficial effect of the above-mentioned method is that the molecular fragments containing catechol structure selected in this invention have good oxidative cross-linking ability and biocompatibility, and can form a molecular network through oxidative cross-linking, while endowing macromolecular monomers with cross-linking ability and bioadhesion properties.

[0021] A method for synthesizing the above-mentioned macromonomer containing a photo-controlled bond-breaking unit specifically includes the following steps:

[0022] (1) Construction of photosensitive intermediate: Synthesize intermediate A containing photoresponsive breakage functional groups;

[0023] (2) Coupling with catechol compounds: Intermediate A is coupled with a molecular fragment containing a catechol structure (through ester bond, amide bond or carbamate bond) to obtain photosensitive adhesion small molecular structural unit B;

[0024] (3) Connection with functionalized polymers: Photosensitive adhesion small molecular structural unit B and polymer chains containing active functional groups (amino groups) (such as PEG-NH2) are coupled in a solvent under the catalysis of a condensing agent to obtain a macromonomer containing photocontrolled bond-breaking units.

[0025] Furthermore, in step (3) above, the condensing agent is at least one of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylurea hexafluorophosphate / N,N-diisopropylethylamine (HBTU / DIPEA), 1-ethyl-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide (EDC / NHS), N,N'-dicyclohexylcarbodiimide / 1-hydroxybenzotriazole (DCC / HOBt), 1,1'-carbonyldiimidazole (CDI), and triphosgene (BTC).

[0026] Furthermore, in step (3) above, the solvent is at least one of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and N-methylpyrrolidone (NMP).

[0027] The present invention also claims the use of a macromonomer containing a photo-controlled bond-breaking unit or a macromonomer containing a photo-controlled bond-breaking unit prepared by the above-described synthesis method in the preparation of functional hydrogels or interface materials.

[0028] The macromonomers containing photo-controlled bond-breaking units of this invention have good application scalability and can be used to construct functional hydrogels or interface materials with photoresponsiveness and / or adhesion. Specific applications include:

[0029] (1) Construct photoresponsive adhesive hydrogels to achieve interface fixation and photoinduced controllable debonding in a humid environment;

[0030] (2) Achieve surface functionalization modification of interfaces such as metal, rubber, plastic, and biological tissue;

[0031] (3) It is applied to drug controlled release systems, implantable medical devices, flexible electronic device connection layers and peelable packaging fields.

[0032] In particular, the hydrogel material constructed from macromolecular monomers containing photo-controlled bond-breaking units of the present invention can achieve rapid gel-sol transformation or structural disintegration under the action of exogenous ultraviolet light, which is suitable for non-invasive removal after biological implantation and reduces the risk of postoperative tissue damage and secondary inflammation.

[0033] As can be seen from the above technical solution, compared with the prior art, the beneficial effects of the present invention are as follows:

[0034] 1. Highly integrated functionality, with a clear and controllable structural design.

[0035] The design adopts a three-segment modular structure (polymer backbone + photo-responsive fracture unit + adhesion group), which allows for flexible adjustment of the molecular structure and properties of monomers according to application requirements, realizing the design concept of "structure-function integration".

[0036] 2. Controllable photoresponsive degradation behavior

[0037] By introducing photosensitive units such as o-nitrobenzyl ester and coumarin, the macromolecular monomers can be broken under ultraviolet light of a specific wavelength of 300-405nm, giving the constructed hydrogel material a time- and space-controllable degradation capability, which is suitable for high-precision application scenarios such as intelligent release and peelable encapsulation.

[0038] 3. Excellent underwater adhesion and biocompatibility

[0039] The adhesion end groups introduce molecules containing catechin structures such as dopamine and catechin, enabling macromolecular monomers to achieve strong and bio-friendly adhesion even in humid environments, making them particularly suitable for the fixation and encapsulation of biological tissue interfaces and implantable materials.

[0040] 4. Synthetic strategies with mild reaction conditions and high versatility

[0041] Using standard condensation reaction systems (such as EDC / NHS, HBTU / DIPEA), it is suitable for a variety of solvents and reaction conditions. The synthesis process is simple and controllable, facilitating industrial scale-up and customized modification.

[0042] 5. Supports multi-scenario application expansion

[0043] The constructed macromonomers can be widely used in the construction of photoresponsive hydrogels, self-adhesive interfaces, intelligent drug release systems, flexible electronic packaging materials, etc., and are applicable to multiple interdisciplinary fields such as medical, materials and electronics, with good application prospects and market transformation potential.

[0044] 6. Promote the development of non-invasive medical procedures

[0045] The constructed macromolecular monomers are particularly suitable for postoperative controllable deadhesion or non-invasive removal of implanted devices, significantly reducing secondary damage and postoperative inflammation caused by traditional surgery, and improving the safety and comfort of clinical operations.

[0046] 7. The photoresponsive cleavage functional groups in the macromonomers containing photocontrolled bond-breaking units of this invention can undergo bond-breaking reactions under ultraviolet light irradiation in the wavelength range of 300-405 nm, thereby causing degradation of the macromolecular backbone or side groups or deconstruction of the network structure. The molecular fragments of the catechol structure have oxidative cross-linking properties and can form stable non-covalent or semi-covalent adhesion interfaces with various material surfaces, enhancing the bioadhesion properties of the hydrogel.

[0047] 8. This invention proposes a macromonomer design strategy containing photo-controlled bond-breaking units. By organically combining a polymer chain, a photoresponsive bond-breaking functional group, and a catechol-containing adhesion group in a three-segment manner, a functional monomer with both photodegradability and bioadhesion is constructed, which can then be used to construct photo-controllable degradable hydrogel materials. This strategy not only improves the functional integration of materials but also provides a new technical path for the application of bioadhesion materials in flexible devices, bio-encapsulation, and tissue engineering.

[0048] 9. The macromonomer containing the photo-controlled bond-breaking unit of the present invention has controllable photoresponsive degradation characteristics and bioadhesion ability, and is suitable for constructing functional hydrogel materials with photoresponsive degradation behavior. It can be widely used in a variety of biomedical and smart material applications such as biological tissue adhesion, controllable debonding, flexible device encapsulation, drug release and implantable electronic devices.

[0049] 10. The macromonomer containing the photo-controlled bond-breaking unit of the present invention can be used to construct functional hydrogels or interface materials with photoresponsiveness and / or adhesion, realize the functional modification of biological tissue surfaces or interfaces of various substrates (such as metals, plastics, and rubber), and be applied in the fields of drug controlled release, implantable devices, flexible electronics, and peelable interface encapsulation.

[0050] 11. The hydrogel constructed from macromolecular monomers containing photo-controlled bond-breaking units of the present invention has photo-induced controllable debonding properties, which is suitable for non-invasive removal or degradation by external light after implantation on the tissue surface, reducing the risk of postoperative tissue damage and secondary inflammation.

[0051] In summary, the photoresponsive modified macromonomers of this invention exhibit significant technical advantages in terms of structural-functional integration, responsive performance regulation, bio-interface adhesion, and application diversity. They have broad application prospects and promotional value, and are particularly suitable for cutting-edge interdisciplinary fields such as smart hydrogel materials, bioadhesives, tissue engineering scaffolds, and flexible implantable electronic devices. Attached Figure Description

[0052] Figure 1 The 1H NMR spectrum of intermediate 1 in Example 1;

[0053] Figure 2 For intermediate 2 of Example 1 1 H NMR spectrum;

[0054] Figure 3 For intermediate 3 of Example 1 1 H NMR spectrum;

[0055] Figure 4 For intermediate 4 of Example 1 1 H NMR spectrum;

[0056] Figure 5 The 1H NMR spectrum of intermediate 5 in Example 1;

[0057] Figure 6 For Example 1, PEG-SO2CH3 1 H NMR spectrum;

[0058] Figure 7 For Example 1, PEG-NH2 1 H NMR spectrum

[0059] Figure 8 For Example 1, the PEG-o-NB-DA macromonomer 1 H NMR spectrum;

[0060] Figure 9 The UV absorption spectra of o-NB-DA small molecule (a) and PEG-o-NB-DA macromonomer (b) in Example 1 change with light irradiation time;

[0061] Figure 10 The mass spectrometry changes of o-NB-DA small molecule (a) and PEG-o-NB-DA macromonomer (b) before and after irradiation in Example 1;

[0062] Figure 11 Photographs of the gel-sol transition were generated using photogel illumination as an application example.

[0063] Figure 12 The results of photorheological testing of gels are an example of the application.

[0064] Figure 13 The results of the overlap-shear adhesion test of the gel on different substrates are shown in the example.

[0065] Figure 14 The results of overlap-shear adhesion tests of the gel on different substrates before and after light exposure are shown in the example. Detailed Implementation

[0066] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0067] Example 1

[0068] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0069] (1) Vanillin ethyl ketone (30 g, 180.5 mmol) was dissolved in 150 mL of anhydrous DMF, and ethyl 4-bromobutyrate (31 mL, 217 mmol) and potassium carbonate (37.4 g, 271 mmol) were added sequentially. The mixture was stirred overnight under a nitrogen atmosphere. After the reaction was completed, the reaction solution was poured into 2 L of ice water to settle. The mixture was stirred at room temperature for 2 h and then allowed to stand overnight at 4 °C. The precipitate was filtered and dried under vacuum to obtain intermediate 1 (ethyl 4-(4-acetyl-2-methoxyphenoxy)butyrate) with a yield of 95%.

[0070] (2) Intermediate 1 (25g, 89mmol) was added in portions to 70mL of 70% concentrated nitric acid pre-cooled under ice bath conditions, and the temperature was controlled not to exceed 35℃. After reacting at 32℃ for 1h, it was added dropwise to deionized water at 4℃ to precipitate. After stirring, standing and filtration, intermediate 2 (nitrated product) was obtained. After recrystallization from ethanol, a pale yellow solid was obtained with a yield of 60%.

[0071] (3) Dissolve intermediate 2 (6.36 g, 19.5 mmol) in ethanol (100 mL), bubble nitrogen gas at 38 °C, slowly add sodium borohydride (0.459 g, 12.1 mmol), stir overnight to obtain a red solution; precipitate and filter to obtain yellow powder intermediate 3 (reduction product), yield 62%;

[0072] (4) Intermediate 3 (3.58 g, 10.9 mmol) was dissolved in 15 mL of anhydrous pyridine to remove water by azeotropic reaction, then dissolved in 30 mL of anhydrous DCM (dichloromethane), and CDI (2.66 g, 16.4 mmol) was added. After stirring at room temperature in the dark for 2.5 h, dopamine hydrochloride (6.22 g, 32.8 mmol) and triethylamine (5.32 mL, 38.3 mmol) were added, and the mixture was reacted in 20 mL of anhydrous DMF for 24 h. After removing the solvent by rotary evaporation, the mixture was purified by silica gel column chromatography (methanol / DCM = 1:4) to obtain orange solid intermediate 4 (the product after amide coupling), with a yield of 66%.

[0073] (5) Intermediate 4 (4.89 g, 9.7 mmol) and sodium hydroxide (0.57 g, 14.5 mmol) were dissolved in EtOH / H2O (3:1, 50 mL), stirred overnight at room temperature, the solvent was removed by rotary evaporation, and the solution was redissolved in water and the pH was adjusted to ~4. After centrifugation and washing, brown solid intermediate 5 (o-nitrobenzyl ester dopamine photosensitive small molecule o-NB-DA) was finally obtained with a yield of 60%.

[0074] (6) PEG (Mn = 6000, 10 g, 1.66 mmol) and triethylamine (5.54 mL, 40 mmol) were dissolved in 120 mL of anhydrous DCM and stirred in an ice bath; methanesulfonyl chloride (3.6 mL, 46.5 mmol) was dissolved in 40 mL of anhydrous DCM and added slowly at a dropping rate of 2 h, and the reaction was continued in an ice bath for 48 h; after the reaction was completed, deionized water and DCM (100 mL: 40 mL) were added, and the phases were separated using a separatory funnel. The organic phase was washed successively with 1 N HCl and saturated NaCl, dried, and precipitated to obtain PEG-SO2CH3 (9.7 g), with a yield of 97%;

[0075] (7) Dissolve PEG-SO2CH3 in 300 mL of concentrated ammonia water, add ammonium chloride (35.5 g, 663.8 mmol), and react at room temperature for 48 h; after adding NaCl (36 g), extract with DCM, dry the organic phase and precipitate to obtain PEG-NH2 (9.5 g), with a yield of 95%;

[0076] (8) Intermediate 5 (2.65 g, 5.54 mmol) was dissolved in 20 mL of anhydrous DMF, and HBTU (2.1 g, 5.54 mmol) and DIPEA (0.96 mL, 5.54 mmol) were added. PEG-NH2 (10.13 g, 1.68 mmol) was dissolved in 10 mL of DMF and slowly added to the above reaction solution. The reaction was carried out at room temperature for 48 h. The reaction solution was diluted with DCM and washed successively with saturated NaHCO3, 1N HCl and saturated NaCl solution. After drying and concentration, a yellow solid was precipitated. After dissolving in deionized water, the solid was dialyzed for 3 days (MWCO = 3500) and finally freeze-dried to obtain PEG-o-NB-DA (9.5 g), with a yield of 95%.

[0077] Example 2

[0078] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0079] (1) Weigh 4-hydroxycoumarin (6.0 g, 33.3 mmol) and dissolve it in 100 mL of anhydrous DMF. Add 4-bromobutyric acid (4.5 mL, 39.6 mmol) and potassium carbonate (6.0 g, 43.5 mmol). Stir the mixture at room temperature for 24 h under a nitrogen atmosphere. Pour the reaction solution into 300 mL of ice water to precipitate the precipitate. Filter and dry to obtain a pale yellow solid 4-hydroxycoumarin butyrate, with a yield of 88%.

[0080] (2) The above coumarin butyrate (3.0 g, 11 mmol) and epicatechin (5.2 g, 18.4 mmol) were dissolved in 50 mL of anhydrous DMF, and EDC·HCl (3.8 g, 19.8 mmol), NHS (2.3 g, 19.8 mmol) and triethylamine (3.0 mL, 21.5 mmol) were added. The mixture was reacted at room temperature in the dark for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation to obtain a viscous orange intermediate, which was purified by silica gel column chromatography to obtain a solid product.

[0081] (3) Dissolve the four-arm PEG-NH2 (Mn≈10,000Da, 10g, 1.0mmol) in 100mL of anhydrous DMSO;

[0082] (4) Dissolve the solid product (1.5g) from step (2) in 20mL of DMF, add HBTU (1.1g, 2.9mmol) and DIPEA (0.5mL, 2.9mmol) and mix to activate for 10min, then slowly add to PEG-NH2 solution and react at room temperature for 48h.

[0083] (5) The reaction solution was diluted with DCM, washed successively with 1N HCl, saturated NaHCO3 and saturated NaCl solution, dried, concentrated by rotary evaporation and precipitated to obtain a yellow solid;

[0084] (6) The yellow solid was dissolved in deionized water and dialyzed for 3 days using a MWCO 3500 dialysis bag, with water changed 4 times a day. After freeze drying, a four-armed PEG-coumarin-epicatechin macromonomer was obtained with a yield of 88%.

[0085] Example 3

[0086] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0087] (1) o-Nitrobenzyl acid (4.20 g, 23.0 mmol), NHS (2.65 g, 23.0 mmol) and EDC·HCl (4.41 g, 23.0 mmol) were added to 50 mL of anhydrous DMF and stirred at room temperature for 2 h to activate the mixture; then tannic acid (5.30 g, 11.5 mmol) was added and the reaction was continued for 24 h to obtain intermediate C (tannic acid derivative containing o-NB structure) with a yield of 72%;

[0088] (2) Dissolve PCL2000-PEG2000-NH2 block copolymer (10.00 g, terminal amino content about 2.0 mmol) in 50 mL of anhydrous DMSO, add intermediate C (2.80 g, about 3.5 mmol), HBTU (1.33 g, 3.5 mmol) and DIPEA (0.61 mL, 3.5 mmol), and react at room temperature for 48 h;

[0089] (3) The reaction solution was diluted with DCM and washed sequentially with saturated NaHCO₃, 1N HCl and saturated NaCl aqueous solution. After drying, the product was dissolved in deionized water and dialyzed for 72 h using a MWCO 10,000 dialysis bag. After freeze drying, the PCL-PEG-oNB-tannic acid macromonomer was obtained with a yield of about 85%.

[0090] Example 4

[0091] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0092] (1) Coumarin-carboxylic acid (5.50 g, 22.0 mmol) and NHS (2.53 g, 22.0 mmol) and EDC·HCl (4.22 g, 22.0 mmol) were added to anhydrous DMF (60 mL), stirred and activated for 2 h, and then catechin (3.00 g, 10.3 mmol) was added. The mixture was reacted at room temperature for 24 h to obtain intermediate D (coumarin-catechin structure) with a yield of 75%.

[0093] (2) Weigh PVA (Mn≈30,000, 10.00g) and dissolve it in 150mL of distilled water. Add sodium hydroxide (0.30g) to adjust the pH to 11. Slowly add epichlorohydrin (1.50mL, 19.3mmol) and stir the reaction at 50℃ for 12h to obtain amino-modified PVA product.

[0094] (3) The amino-modified PVA product was dissolved in 30 mL of DMSO and reacted with intermediate D (2.00 g) in an EDC / NHS (1.0 mmol each) system for 24 h.

[0095] (4) The reaction solution was dialyzed (MWCO 3500) for 72 h and then freeze-dried to obtain PVA-coumarin-catechin macromonomer.

[0096] Example 5

[0097] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0098] (1) The terminal hydroxyl groups of PLGA-PEG-PLGA triblock copolymer (PLGA 3000-PEG 2000-PLGA 3000, 10.00 g) were converted to amino groups: dissolved in dry THF (100 mL), methanesulfonyl chloride (1.50 mL, 19.4 mmol) and TEA (2.00 mL, 14.4 mmol) were added, and the mixture was reacted in an ice bath for 2 h. Then, ammonia water (30%, 50 mL) was added, and the mixture was stirred for 24 h to obtain PLGA-PEG-PLGA-NH2 with a yield of 92%.

[0099] (2) o-Nitrobenzyl acid (2.30 g, 12.5 mmol) and protocatechuic acid (2.10 g, 13.0 mmol) were reacted in DMF in the presence of EDC / NHS (12.5 mmol each) for 24 h to obtain intermediate E;

[0100] (3) Intermediate E (2.00 g) and PLGA-PEG-PLGA-NH2 (10.00 g) were reacted for 48 h under the conditions of HBTU (3.2 mmol) and DIPEA (0.56 mL). The product was dialyzed (MWCO 10,000) and then freeze-dried to obtain PLGA-PEG-PLGA-oNB-protocatechuic acid monomer.

[0101] Example 6

[0102] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0103] (1) Dissolve chitosan (5.00 g, degree of deacetylation > 80%) in 0.1% acetic acid aqueous solution (100 mL) and stir at room temperature for 12 h to form a homogeneous solution;

[0104] (2) Azelaic acid (2.50 g, 13.4 mmol) and hydroxylamine hydrochloride (1.50 g, 21.6 mmol) were reacted in water, the pH was adjusted to 5.5, and the mixture was stirred at 60 °C for 4 h to obtain intermediate F (O-acyloxime-carboxylic acid);

[0105] (3) Intermediate F (1.50 g) was coupled with catecholamine (1.10 g) in an EDC / NHS system and reacted for 16 h to obtain intermediate G;

[0106] (4) Intermediate G (2.00 g) was mixed with chitosan solution, and EDC (2.40 g) and NHS (1.40 g) were added at pH 6.5. The mixture was stirred at room temperature for 24 h, dialyzed (MWCO 12,000) for 3 days, and then freeze-dried to obtain chitosan-O-acyloxime-catecholamine monomer.

[0107] Example 7

[0108] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0109] (1) Dissolve POEGMA (Mn≈20,000, 5.00 g, containing terminal amino group) in DMF (50 mL), add o-nitrobenzyl ester-dopamine (o-NB-DA, 2.00 g, about 4.0 mmol), then add EDC (0.77 g) and NHS (0.46 g), and react for 24 h;

[0110] (2) The reaction solution was precipitated with diethyl ether, resuspended in water, dialyzed (MWCO 3500) for 3 days and then freeze-dried to obtain the POEGMA-oNB-DA macromonomer with a yield of 83%.

[0111] Example 8

[0112] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0113] (1) Coumarin-carboxylic acid (4.50 g) and protocatechuic acid (2.50 g) were reacted in DMF with EDC (2.30 g) and NHS (1.40 g) for 24 h to obtain intermediate H;

[0114] (2) Dissolve branched PEI (Mw≈25,000, 10.00g) in 50mL of DMSO / water mixed solvent, add intermediate H (2.00g) dropwise, adjust the pH to 8.0, and add DIPEA (1.00mL);

[0115] (3) The reaction was carried out at room temperature for 48 hours, the reaction solution was dialyzed (MWCO 12,000) for 3 days, and then freeze-dried to obtain PEI-coumarin-protocatechuic acid macromonomer.

[0116] Example 9

[0117] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0118] (1) D,L-lactide (10.00g, 69.4mmol) and glycolic acid (0.50g) were polymerized under vacuum at 120℃ for 8h under Sn(Oct)2 (50mg) catalysis to obtain hydroxyl-terminated polylactic acid (PLA-OH, Mn≈4000);

[0119] (2) PLA-OH (5.00 g) was activated in DCM with methanesulfonyl chloride (1.20 mL) and then ammonolyzed to obtain PLA-NH2 (yield 90%).

[0120] (3) Reaction of o-nitrobenzyl acid with catecholamine yields o-NB-DHC intermediate (refer to Example 1);

[0121] (4) The o-NB-DHC intermediate was condensed with PLA-NH2 in CDI / DMF for 24 h, and then freeze-dried after column chromatography to obtain the PLA-oNB-catecholamine macromonomer.

[0122] Example 10

[0123] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0124] (1) Dissolve hydroxyethyl cellulose (HEC, Mw≈100,000, 5.00 g) in 100 mL of 0.1 M NaOH solution and stir for 30 min in a water bath at 70 °C to form a homogeneous solution;

[0125] (2) After cooling to room temperature, potassium carbonate (3.00 g, 21.7 mmol) and p-toluenesulfonyl chloride (2.00 g, 10.5 mmol) were added dropwise under ice bath, and the reaction temperature was controlled below 10 °C. The reaction was carried out for 6 h. After the reaction, cold ethanol (200 mL) was added to precipitate the solid, and the solid was collected by centrifugation to obtain TsHEC intermediate.

[0126] (3) Weigh out 2.00 g of TsHEC intermediate and dissolve o-nitrobenzyl ester-dopamine small molecule (o-NB-DA, 1.00 g) in 30 mL of DMSO, add 0.5 mL of triethylamine, and stir at room temperature for 24 h.

[0127] (4) After the reaction was completed, cold ethanol was added to precipitate the product, which was then redissolved in deionized water, dialyzed (MWCO 10,000) for 3 days, and freeze-dried to obtain the HEC-oNB-DA macromonomer with a yield of 78%.

[0128] Example 11

[0129] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0130] (1) Coumarin-carboxylic acid (3.00g) and catechin (2.00g) were added to DMF, along with EDC (2.10g) and NHS (1.30g). The mixture was stirred at room temperature for 24h to obtain a small molecule intermediate of coumarin-catechin.

[0131] (2) Acrylamide (10.00g) and coumarin-catechin small molecule intermediate (2.50g) were dissolved in a water / ethanol mixed solvent (1:1, 50mL) at a molar ratio of 3:1. APS (ammonium persulfate, 50mg) and TEMED (50μL) were added and polymerized at room temperature for 6h.

[0132] (3) After the reaction solution was cooled, excess ethanol was added to precipitate the product, which was then redissolved in water and dialyzed (MWCO 12,000) for 3 days. The product was then freeze-dried to obtain the PAM-coumarin-catechin copolymer monomer with a yield of 71%.

[0133] Example 12

[0134] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0135] (1) Dissolve gelatin (Type B, 10.00 g) in PBS buffer (100 mL, pH 7.4) and stir in a 40°C water bath for 30 min to obtain gelatin solution;

[0136] (2) Dissolve o-nitrobenzyl ester-protocatechuic acid small molecules (2.50 g) in DMF (10 mL), add EDC (1.92 g) and NHS (1.16 g) to activate the reaction for 1 h to obtain the activated solution;

[0137] (3) The activation solution was added dropwise to the gelatin solution and the reaction was continued for 24 hours under the dark at room temperature. After the reaction, the solution was dialyzed for 3 days using a dialysis bag (MWCO 12,000) and then freeze-dried to obtain gelatin-oNB-protocatechuic acid monomer with a yield of about 69%.

[0138] Example 13

[0139] The method for synthesizing macromonomers containing photo-controlled bond-breaking units specifically includes the following steps:

[0140] (1) Bisphenol A (5.00 g) and diphenyl carbonate (6.20 g) were polymerized at 180 °C for 6 h under Sn(Oct)2 catalysis to obtain hydroxyl-terminated polycarbonate (PC-OH, Mn≈4000);

[0141] (2) Dissolve PC-OH (3.00 g) in anhydrous DCM, add methanesulfonyl chloride (0.90 mL) and TEA (1.20 mL), react under ice bath for 2 h, then add concentrated ammonia (30 mL), stir and react for 12 h to obtain PC-NH2;

[0142] (3) PC-NH2 (2.50 g) and o-NB-DA (1.20 g) were reacted in DMF in the presence of HBTU (1.14 g) / DIPEA (0.40 mL) for 48 h. The post-treatment was the same as in the previous example. The PC-oNB-DA macromonomer was obtained by freeze drying with a yield of about 74%.

[0143] Application examples

[0144] Based on Example 1, a photoresponsive hydrogel was prepared using the PEG-o-NB-DA macromonomer, and the specific process is as follows:

[0145] (1) Weigh 200 mg of PEG-o-NB-DA (Mw = 5000), add it to 0.9 mL of PBS buffer, shake and mix well to completely dissolve it, forming a viscous, transparent monomer precursor solution;

[0146] (2) Take another 0.1 mL of 5.4 wt% sodium periodate aqueous solution and add it quickly to the monomer precursor solution. Mix thoroughly immediately and let the mixture stand at room temperature for about 15 seconds.

[0147] (3) The gelation process is completed in about 2 minutes, forming a stable light brown transparent hydrogel with good self-supporting properties.

[0148] Performance testing

[0149] 1. Product Characterization

[0150] Based on Example 1, the products after each reaction step were characterized using 1H NMR spectroscopy to verify the structural correctness of each intermediate and the final product. The testing instrument was a Bruker 400MHz NMR, and the solvent was DMSO-d6 or CDCl3. The results are as follows: Figure 1-8 As shown.

[0151] in, Figure 6-7 This indicates that the terminal group has been successfully converted; Figure 8 This indicates that the modification was successful. The key chemical shift peaks and integral ratios in the spectrum are consistent with the expected structure, indicating that each reaction step was successful.

[0152] 2. UV irradiation test

[0153] Based on Example 1, the o-NB-DA small molecule and the PEG-o-NB-DA macromonomer were respectively formulated into 0.5×10⁻⁶ ppm solutions. -4 The absorption changes of solution M under 365nm UV irradiation were recorded using a UV spectrophotometer (UV-2600, Shimadzu).

[0154] The results are as follows Figure 9-10 As shown. Among them, Figure 9 It shows an ultraviolet absorption peak (λ). max The wavelength (≈365nm) decreases with irradiation time, indicating that photoresponse dissociation occurs. Figure 10 The corresponding degradation products show clear structures and correspond well to theoretical values.

[0155] 3. Gel photorheological test

[0156] Based on the application example, the gel was irradiated with ultraviolet light, and the gel's state before and after irradiation was photographed. The photographs of the gel in different states are summarized as follows: Figure 11 As shown.

[0157] Depend on Figure 11 It can be seen that the gel in the glass bottle can transform into a fluid sol state after being exposed to ultraviolet light for about 20 minutes, indicating the gel's ability to respond to ultraviolet light phase transition.

[0158] 4. Gel rheological testing

[0159] Based on the application example, rheological tests were performed on the gel. The specific process is as follows: A quartz plate with a diameter of 20 mm and connected to an illumination accessory was selected as the rheometer. Approximately 0.5 mL of the pre-gel solution from step (2) was pipetted onto the plate rheometer. The plate spacing was then controlled to be 1 mm, and the edges were sealed with dimethyl silicone oil to prevent evaporation during the gel test. The specific test parameters of the instrument were: strain time scan (f = 1 Hz, strain = 0.5%). After obtaining relatively stable data results for 25 s of scanning, the gel was illuminated with 365 nm ultraviolet light for 200 s, during which time data acquisition was continuously performed. The final results are as follows: Figure 12 As shown.

[0160] Depend on Figure 12 It can be seen that within 20 seconds after the start of light irradiation, the storage modulus G', which reflects the solid properties of the gel, and the energy dissipation modulus G”, which reflects the liquid properties of the gel, reversed. This proves from the perspective of rheological properties that the gel has gel-sol phase transition characteristics after being exposed to ultraviolet light.

[0161] 5. Gel overlap-shear adhesion test

[0162] Based on the application example, an overlap-shear adhesion test was performed on the gel. The specific process is as follows: The pre-gel solution in step (2) was evenly spread on the surface of a clean and dry glass slide, while a slight pressure was applied with another glass slide to ensure complete contact at the interface, forming a sandwich structure; after standing for 30 minutes, it was observed that a stable adhesion interface was formed between the two glass slides through the gel, and the other glass slide did not fall off after one of the glass slides was flipped, showing good adhesion ability; then the adhesion force was tested with an electronic universal testing machine, and the adhesion strength and interface toughness were calculated based on the adhesion area; subsequently, the glass slides were replaced with polystyrene plastic sheets, copper sheets, PDMS silicone rubber sheets, and pigskin, and the above operation was repeated. The final results are summarized as follows. Figure 13 As shown.

[0163] Depend on Figure 13 It is known that gels have high adhesion strength and interfacial toughness on various substrate surfaces.

[0164] 6. Gel overlap-shear adhesion test before and after light exposure A

[0165] Based on the application example, an overlap-shear adhesion test was conducted on the gel before and after light irradiation. The specific process is as follows: The pre-gel solution in step (2) was evenly spread on the surface of a clean and dry glass slide, while a slight pressure was applied with another glass slide to ensure complete contact at the interface, forming a sandwich structure; after standing for 30 minutes, it was observed that a stable adhesion interface was formed between the two glass slides through the gel, and the other glass slide did not fall off after one of the glass slides was flipped, showing good adhesion ability; then, the gel surface was irradiated with 365nm ultraviolet light for 2 minutes, and the gel was observed to gradually transform from a gel state to a sol state, and the edges of the non-clamped glass slides began to loosen and shrink; then, the adhesion force was tested with an electronic universal testing machine, and the adhesion strength and interface toughness were calculated based on the adhesion area; then, the glass slide was replaced with a polystyrene plastic sheet, and the above operation was repeated with a PDMS silicone rubber sheet. The final results are summarized as follows. Figure 14 As shown in the first three groups.

[0166] Depend on Figure 14 It can be seen that the bonding strength of the gel between two identical substrates of the three different types listed can be controlled by light irradiation. After ultraviolet light irradiation, the bonding strength decreased significantly.

[0167] 7. Gel overlap-shear adhesion test before and after light exposure B

[0168] Based on the application example, an overlap-shear adhesion test was conducted on the gel before and after light irradiation. The specific process is as follows: The pre-gel solution in step (2) was evenly spread on the surface of a clean and dry PDMS silicone rubber sheet. At the same time, a copper sheet was used to apply slight pressure to ensure complete contact of the interface, forming a sandwich structure. After standing for 30 minutes, it was observed that a stable adhesion interface was formed between the two different sheets through the gel. When one glass sheet was flipped, the other sheet did not fall off, showing good adhesion ability. Then, 365nm ultraviolet light was used to irradiate the gel surface through the transparent side of the PDMS silicone rubber sheet for 2 minutes. The gel was observed to gradually transform from a gel state to a sol state. The edge of the non-clamped side of the PDMS silicone rubber sheet began to loosen and shrink. Then, the adhesion force was tested using an electronic universal testing machine, and the adhesion strength and interface toughness were calculated based on the adhesion area. The copper sheet was then replaced with pigskin and the above operation was repeated. The final results are summarized as follows. Figure 14 (The last two groups are shown.)

[0169] Depend on Figure 14 It can be seen that the bonding strength of the gel between two different substrates of the two different types listed can be controlled by light irradiation. After ultraviolet light irradiation, the bonding strength decreased significantly.

[0170] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A macromolecular monomer containing a photo-controlled bond-breaking unit, characterized in that, It is composed of polymer chains, photoresponsive cleavage functional groups, and molecular fragments containing catechol structures covalently linked by chemical bonds.

2. The macromolecular monomer containing a photo-controlled bond-breaking unit according to claim 1, characterized in that, The polymer chain is at least one of hydrophilic polymers, amphiphilic polymers, and hydrophobic polymers.

3. A macromolecular monomer containing a photo-controlled bond-breaking unit according to claim 2, characterized in that, The hydrophilic polymer is at least one of polyethylene glycol, polyvinyl alcohol, hydroxyethyl cellulose, polyacrylamide, polyethyleneimine, gelatin, chitosan, and hyaluronic acid. The amphiphilic polymer is at least one of the following: polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer, poly(polyethylene glycol methacrylate), polycaprolactone-polyethylene glycol block copolymer, and poly(lactic acid-glycolic acid)-polyethylene glycol-poly(lactic acid-glycolic acid) triblock copolymer; The hydrophobic polymer is at least one of polylactic acid, polycaprolactone, polycarbonate, and aliphatic polyester.

4. A macromolecular monomer containing a photo-controlled bond-breaking unit according to any one of claims 1-3, characterized in that, The polymer chain is at least one of linear polyethylene glycol, three-arm polyethylene glycol, four-arm polyethylene glycol, and eight-arm polyethylene glycol, with a number average molecular weight of 1,000-50,000 Daltons.

5. A macromolecular monomer containing a photo-controlled bond-breaking unit according to claim 1, characterized in that, The photoresponsive cleavage functional group is at least one selected from o-nitrobenzyl ester, coumarin, O-acyl oxime, anthracene, thymine, and O-acyl oxime.

6. A macromolecular monomer containing a photo-controlled bond-breaking unit according to claim 1, characterized in that, The molecular fragment containing the catechin structure is at least one of dopamine, catechin, epicatechin, protocatechuic acid, catechin amine, and tannic acid.

7. A method for synthesizing a macromonomer containing a photo-controlled bond-breaking unit as described in any one of claims 1-6, characterized in that, Specifically, the following steps are included: (1) Synthesize intermediate A containing photoresponsive fracture functional groups; (2) Intermediate A was coupled with a molecular fragment containing a catechol structure to obtain photosensitive adhesion small molecular structural unit B. (3) The photosensitive adhesion small molecular structural unit B and the polymer chain containing active functional groups are coupled in a solvent under the catalysis of a condensing agent to obtain the macromonomer containing the photocontrolled bond breaking unit.

8. The method for synthesizing a macromonomer containing a photo-controlled bond-breaking unit according to claim 7, characterized in that, In step (3), the condensing agent is at least one of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylurea hexafluorophosphate / N,N-diisopropylethylamine, 1-ethyl-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide, N,N'-dicyclohexylcarbodiimide / 1-hydroxybenzotriazole, 1,1'-carbonyldiimidazole and triphosgene.

9. The method for synthesizing a macromonomer containing a photo-controlled bond-breaking unit according to claim 7, characterized in that, In step (3), the solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide and N-methylpyrrolidone.

10. The use of a macromonomer containing a photo-controlled bond-breaking unit as described in any one of claims 1-6, or a macromonomer containing a photo-controlled bond-breaking unit prepared by the synthesis method as described in any one of claims 7-9, in the preparation of functional hydrogels or interface materials.

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