A hydrogel that undergoes photoinduced shrinkage under neutral conditions and a method for preparing the same

Abstract

The application discloses a hydrogel which is photo-induced to shrink under neutral conditions and a preparation method thereof, relates to the technical field of hydrogels, and the raw materials for preparing the hydrogel comprise the following components: a photoswitch A3 molecule, N-isopropyl acrylamide, N,N'-methylene bisacrylamide and deionized water. The application designs and synthesizes a polymerizable photoswitch A3 molecule with a high pKa (about 7.66), and covalently grafts the photoswitch A3 molecule into a high-molecular hydrogel. The hydrophilic and hydrophobic property changes caused by the on-off ring isomerization of the photoswitch A3 molecule under neutral pH conditions are utilized to realize the photo-induced volume shrinkage of the hydrogel under neutral conditions, the dependence of the photo-responsive hydrogel material on an acidic environment in the actuation process is overcome, the pH range of the application of the photo-responsive hydrogel is expanded, and biomedical applications under neutral and physiological environments are expected.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of hydrogel, in particular to a hydrogel which occurs photo-induced shrinkage under neutral conditions and a preparation method thereof. BACKGROUND

[0002] Spiropyrans are a class of important research and application value of light-controlled molecular switch, with open ring and closed ring two isomers, which is a class of important research and application value of light-controlled molecular switch, in which the closed ring structure is non-polar, non-charged, colorless, and the open ring structure is polar, charged, colored, the huge difference between the two in nature determines that spiropyrans have very wide application in photochromism, detection imaging, analysis sensing, dynamic materials and many other fields. Under the condition of light, spiropyrans as light switch molecules can change from open ring protonated chlorin form to closed ring spiro form, so that the net charge of the polymer material grafted with spiropyrans changes, affecting the hydrophilic and hydrophobic properties of the polymer chain, thereby realizing the shrinkage or swelling of the hydrogel material. According to the change of the charged nature of spiropyrans after light, it can be divided into photo-induced shrinkage and photo-induced swelling two effects, and spiropyrans hydrogel is applied to photo-induced biomimetic deformation, movement and soft robot fields.

[0003] The light penetration of spiropyrans hydrogel in the thickness direction needs a certain time, which leads to the difference between the photoisomerization degrees of the front and back of the gel under light, the net charge of the material changes before and after light, and then a certain degree of hydrophilic and hydrophobic gradient is generated, finally driving the anisotropic deformation of the hydrogel. However, the repeated use of spiropyrans light-responsive hydrogel relies on the recovery of the spiro form to the open ring protonated chlorin form, and this recovery needs to rely on the dark environment under acidic conditions, which greatly limits the application scenarios of the material. The recovery of the open ring depends on the acidic environment because the pKa of such molecules is low, which is not conducive to the thermodynamic stability of the open ring form under neutral conditions.

[0004] After traditional spiropyrans are grafted into the material, they need to be treated with acid to return to the open ring protonated chlorin form. The degree of transformation from closed ring to open ring is limited. The photoresponsive deformation process of the hydrogel is related to the open-closed ring process of the open ring protonated chlorin after being irradiated to the closed ring spiropyrans, so the preparation of molecules with stable open ring structure in neutral environment can maximize the use of the charge transformation of the molecules in the closed ring process, and achieve the ideal deformation response effect under neutral pH conditions. In order to overcome the dependence of the photoresponsive properties of spiropyrans hydrogel on acidic environment, Schenning et al. constructed a self-protonated hydrogel which can respond to light under neutral pH conditions by introducing acrylic monomers as proton donors into the hydrogel. However, this design changes the composition of the polymer monomer, and does not fundamentally solve the problem of instability of the open ring form of the molecule under neutral conditions. SUMMARY

[0005] Based on this, it is necessary to provide a hydrogel which occurs photo-induced shrinkage under neutral conditions and a preparation method thereof aiming at the above technical problems.

[0006] In a first aspect, the present application provides a hydrogel which occurs photo-induced shrinkage under neutral conditions, and the raw materials for preparing the hydrogel comprise the following components:

[0007] a photo-switch A3 molecule, N-isopropyl acrylamide, N, N'-methylene bisacrylamide and deionized water;

[0008] The photo-switch A3 molecule is an ionic compound, and the structure of the cationic part of the photo-switch A3 molecule is shown in formula I:

[0009]

[0010] In a second aspect, the present application further provides a preparation method of a hydrogel which occurs photo-induced shrinkage under neutral conditions, and the preparation method comprises:

[0011] S1, preparing an A1 molecule, and the A1 molecule is N-(2-methylbenzothiazole-6-yl) methyl acrylamide;

[0012] S2, based on the A1 molecule, preparing an A2 molecule, and the A2 molecule is hydroxyethyl-functionalized N-(2-methylbenzothiazole-6-yl) methyl acrylamide bromide;

[0013] S3, based on the A2 molecule, preparing a photo-switch A3 molecule;

[0014] S4, based on the photo-switch A3 molecule, preparing a hydrogel.

[0015] Further, the preparation of the A1 molecule comprises:

[0016] S11, mixing 2-methylbenzothiazole-6-amine and triethylamine in dichloromethane, and adding methyl acryloyl chloride drop by drop under ice bath conditions, stirring for 6-8 h to obtain a first mixture;

[0017] S12, adding saturated NaHCO3 aqueous solution to the first mixture, extracting the dichloromethane phase, and after the extraction is completed, drying the first mixture with anhydrous sodium sulfate;

[0018] S13, removing the residual solvent in the dried first mixture by rotary evaporation, and purifying and separating the mixture by column chromatography with an eluent to obtain the A1 molecule in the form of a white powder solid.

[0019] Further, the chemical formula of the preparation of the A1 molecule is:

[0020]

[0021] wherein, represents A1 molecule; represents 2-methylbenzothiazole-6-amine; represents methacryloyl chloride; TEA represents triethylamine; DCM represents dichloromethane.

[0022] Further, the molar ratio of 2-methylbenzothiazole-6-amine, triethylamine and methacryloyl chloride is 1:1.2:1.2, and the eluent used for column purification is n-hexane and ethyl acetate in a volume ratio of 3:1.

[0023] Further, based on A1 molecule, the preparation of A2 molecule includes:

[0024] S21, mixing A1 molecule and 2-bromoethanol in acetonitrile in a molar ratio of 1:3, and reacting at 85-90°C for 3d to obtain a second mixture;

[0025] S22, removing the solvent in the second mixture by rotary evaporation, and then adding dropwise into an ethyl ether solution for precipitation, and then obtaining a light yellow powder through centrifugation and filtration;

[0026] S23, pouring the light yellow powder into deionized water, washing with ethyl acetate, collecting the aqueous phase, and finally removing water by a rotary evaporator to obtain A2 molecule in the form of a light yellow powder.

[0027] Further, the chemical formula of A2 molecule is:

[0028]

[0029] wherein, represents the structure of the cationic part of A2 molecule; represents A1 molecule; represents 2-bromoethanol; CH3CN represents acetonitrile.

[0030] Further, based on A2 molecule, the preparation of photo switch A3 molecule includes:

[0031] S31, mixing A2 molecule, 1H-indazole-7-carboxaldehyde, polymerization inhibitor BHT and catalyst ammonium acetate (NH4OAc) in ethylene glycol in a molar ratio of 1:1.5:0.1:0.2, and reacting at 75-80°C for 2d to obtain a third mixture;

[0032] S32, removing the solvent in the third mixture by rotary evaporation, and then adding dropwise into an ethanol solution for precipitation, and then collecting the filter residue after filtration;

[0033] S33, the filter residue is washed with tetrahydrofuran and acetone, and then collected after centrifugation and filtration to obtain orange yellow powder of the light switch A3 molecule, and the light switch A3 molecule is weighed after drying.

[0034] Further, the chemical formula of the light switch A3 molecule is:

[0035]

[0036] In the formula, represents the structure of the cationic part of the light switch A3 molecule; represents the structure of the cationic part of the A2 molecule; represents 1H-indazole-7-carboxaldehyde; EG represents ethylene glycol.

[0037] Further, based on the light switch A3 molecule, a hydrogel is prepared, which comprises:

[0038] S41, N-isopropyl acrylamide and the light switch A3 molecule are added into a container containing a mixed solvent of N-methyl pyrrolidone and water, dissolved by ultrasonic, and then N, N'-methylene bisacrylamide is added and uniformly mixed to obtain a fourth mixture;

[0039] S42, ammonium persulfate aqueous solution is added into the fourth mixture, and argon is introduced to remove oxygen, then ascorbic acid aqueous solution is added into the fourth mixture under ice bath condition, and uniformly mixed to obtain a prepolymer solution;

[0040] S43, the prepolymer solution is injected into a sandwich glass mold for polymerization, and the molded gel is obtained after being shaped at room temperature for 3-24 h, immersed in ethanol for 2 h, and finally replaced into deionized water, and the hydrogel is obtained after being kept in dark for 48 h.

[0041] The beneficial effects of the present application are as follows: by designing and synthesizing a polymerizable, high-pKa light switch A3 molecule, and covalently grafting it into a high molecular hydrogel, the change of hydrophilic and hydrophobic properties caused by the on-off ring isomerization of the light switch A3 molecule under neutral pH conditions is utilized, the light-induced volume shrinkage of the hydrogel under neutral conditions is realized, the dependence of the actuation process of the light-responsive hydrogel material on the acidic environment is overcome, the pH range of the application of the light-responsive hydrogel is expanded, and biomedical applications in neutral and physiological environments are expected. BRIEF DESCRIPTION OF DRAWINGS

[0042] The drawings described herein are used to provide further understanding of the present application, and form a part of the present application. The schematic embodiments of the present application and their descriptions are used to explain the present application, and do not constitute improper limitations on the present application. In the drawings:

[0043] Figure 1is a flow chart of a preparation method of a water gel which occurs photoinduced shrinkage under neutral conditions according to an embodiment of the present application;

[0044] Figure 2 is a detection schematic diagram of a photo switch A3 molecule sample ultraviolet fiber spectrum instrument according to an embodiment of the present application;

[0045] Figure 3 is a light irradiation / dark recovery kinetics curve of a photo switch A3 molecule according to an embodiment of the present application;

[0046] Figure 4 is a curve diagram of a photo switch A3 molecule fitting pKa according to an embodiment of the present application;

[0047] Figure 5 is a photoinduced shrinkage test device schematic diagram according to an embodiment of the present application;

[0048] Figure 6 is a water gel sample light irradiation to light bending diagram according to an embodiment of the present application. DETAILED DESCRIPTION

[0049] In order to make the objects, technical solutions and advantages of the present application clearer, the present application is further described in detail below with reference to the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application, and are not used to limit the present application.

[0050] The present application provides a water gel which occurs photoinduced shrinkage under neutral conditions, and the preparation raw material of the water gel comprises the following components:

[0051] a photo switch A3 molecule, N-isopropyl acrylamide, N,N'-methylene bisacrylamide and deionized water;

[0052] The photo switch A3 molecule is an ionic compound, and the structure of the cationic part of the photo switch A3 molecule is shown as formula I:

[0053]

[0054] Please refer to Figure 1 The present application also provides a preparation method of a water gel which occurs photoinduced shrinkage under neutral conditions, and the preparation method comprises:

[0055] S1, preparing an A1 molecule, and the A1 molecule is N-(2-methylbenzothiazole-6-yl) methyl acrylamide.

[0056] In the description of the present application, the preparation of the A1 molecule comprises:

[0057] S11, mixing 2-methylbenzothiazole-6-amine and triethylamine in dichloromethane, and adding methacryloyl chloride drop by drop under ice bath condition, stirring for 6-8 h to obtain a first mixture.

[0058] S12, adding saturated NaHCO3 aqueous solution to the first mixture, extracting dichloromethane, and drying the first mixture with anhydrous sodium sulfate after the extraction is completed.

[0059] S13, removing residual solvent in the dried first mixture by rotary evaporation, and separating and purifying the mixture by column chromatography to obtain A1 molecule in the form of white powder.

[0060] In the description of the present application, the chemical formula of A1 molecule is:

[0061]

[0062] In the formula, A1 molecule, 2-methylbenzothiazole-6-amine, methyl methacryloyl chloride, and TEA represents triethylamine, and DCM represents dichloromethane.

[0063] The molar ratio of 2-methylbenzothiazole-6-amine, triethylamine and methyl methacryloyl chloride is 1:1.2:1.2, and the eluent of n-hexane and ethyl acetate in a volume ratio of 3:1 is used for column purification.

[0064] In addition, the yield of A1 molecule is about 70%, and the hydrogen spectrum data of nuclear magnetic resonance and the carbon spectrum data of nuclear magnetic resonance of A1 molecule are as follows:

[0065] 1 H NMR (400 MHz, d6-DMSO) δ (ppm): 9.98 (s, 1H), 8.43 (d, J = 2.0 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.66 (dd, J = 8.8, 2.1 Hz, 1H), 5.83 (s, 1H), 5.54 (d, J = 1.2 Hz, 1H), 2.77 (s, 3H), 1.97 (s, 3H).

[0066] 13 C-NMR (400 MHz, d6-DMSO) δ (ppm): 167.37, 166.07, 149.65, 140.79, 136.54, 135.99, 122.11, 120.58, 119.89, 112.92, 20.13, 19.19.

[0067] S2, based on the A1 molecule, preparing an A2 molecule, the A2 molecule being a hydroxyethyl-functionalized N-(2-methylbenzothiazole-6-yl)methyl acrylamide bromide.

[0068] In the description of the present application, based on the A1 molecule, preparing an A2 molecule includes:

[0069] S21, mixing the A1 molecule and 2-bromoethanol in a molar ratio of 1:3 in acetonitrile, reacting at a condition of 85-90°C for 3d to obtain a second mixture.

[0070] S22, removing the solvent in the second mixture by rotary evaporation, then precipitating by dropwise adding into an ethyl ether solution, and obtaining a light yellow powder through centrifugation and filtration.

[0071] S23, pouring the light yellow powder into deionized water, washing with ethyl acetate, collecting the aqueous phase, and finally removing water by a rotary evaporator to obtain the A2 molecule in the form of a light yellow powder.

[0072] In the description of the present application, the chemical formula of the A2 molecule is:

[0073]

[0074] In the formula, represents the structure of the cationic part of the A2 molecule, represents the A1 molecule, represents 2-bromoethanol, and CH3CN represents acetonitrile.

[0075] In addition, the yield of the A2 molecule is about 70%, and the hydrogen spectrum data and carbon spectrum data of the A2 molecule by nuclear magnetic resonance are as follows:

[0076] 1 H NMR (400 MHz, d6-DMSO) δ (ppm): 10.36 (s, 1H), 8.93 (d, J = 2.0 Hz, 1H), 8.27 (d, J = 9.2 Hz, 1H), 7.97 (dd, J = 9.2, 2.1 Hz, 1H), 5.91 (s, 1H), 5.63 (s, 1H), 4.81 (t, J = 4.9 Hz, 2H), 3.88 (t, J = 4.8 Hz, 2H), 3.18 (s, 3H), 1.99 (s, 3H).

[0077] 13 C-NMR (400 MHz, d6-DMSO) δ (ppm): 176.30, 167.25, 139.86, 138.81, 136.95, 129.74, 122.13, 121.15, 117.13, 114.07, 58.57, 51.96, 18.66, 17.17.

[0078] S3, preparing the light switch A3 molecule based on the A2 molecule.

[0079] In the description of the present application, preparing the light switch A3 molecule based on the A2 molecule includes:

[0080] S31, mixing the A2 molecule, 1H-indazole-7-carboxaldehyde, the polymerization inhibitor BHT and the catalyst ammonium acetate NH4OAc in ethylene glycol, maintaining the condition of 75-80℃ for 2d to obtain a third mixture.

[0081] S32, removing the solvent in the third mixture by rotary evaporation, then adding dropwise into an ethanol solution for precipitation, and then collecting the filter residue after filtration.

[0082] S33, washing the filter residue with tetrahydrofuran and acetone, then collecting the light switch A3 molecule in the form of orange yellow powder after centrifugation and filtration, and weighing after drying.

[0083] In the description of the present application, the chemical formula of the light switch A3 molecule is:

[0084]

[0085] In the formula, represents the structure of the cationic part of the light switch A3 molecule, represents the structure of the cationic part of the A2 molecule, represents 1H-indazole-7-carboxaldehyde, and EG represents ethylene glycol.

[0086] Among them, the molar ratio of the A2 molecule, 1H-indazole-7-carboxaldehyde, the polymerization inhibitor BHT and the catalyst ammonium acetate NH4OAc is 1:1.5:0.1:0.2.

[0087] In addition, the yield of the light switch A3 molecule is about 60%. The hydrogen spectrum data of the nuclear magnetic resonance of the light switch A3 molecule is as follows:

[0088] 1H NMR (400 MHz, d6-DMSO) d (ppm): 13.91 (s, 1H), 13.91 (s, 1H), 10.41 (s, 1H), 8.98 (s, 1H), 8.56 (d, J = 15.8 Hz, 1H), 8.35 - 8.24 (m, 2H), 8.21 (d, J = 7.4 Hz, 1H), 8.10 (d, J = 15.7 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.97 (dd, J = 9.2, 1.8 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 5.94 (s, 1H), 5.66 (s, 1H), 5.10 (s, 2H), 3.91 (s, 2H), 2.00 (s, 3H).

[0089] S4, preparing a hydrogel based on the photo-switchable A3 molecule.

[0090] In the description of the present application, preparing a hydrogel based on the photo-switchable A3 molecule comprises:

[0091] S41, adding N-isopropyl acrylamide and the photo-switchable A3 molecule into a container containing a mixed solvent of N-methyl pyrrolidone and water, dissolving by ultrasonic, then adding N, N'-methylene bisacrylamide and mixing uniformly to obtain a fourth mixture;

[0092] S42, adding an aqueous ammonium persulfate solution to the fourth mixture, and purging argon to remove oxygen, then adding an aqueous ascorbic acid solution to the fourth mixture under ice bath condition, and mixing uniformly to obtain a prepolymer solution;

[0093] S43, injecting the prepolymer solution into a laminated glass mold for polymerization, and then taking out the formed gel after setting for 3-24 h at room temperature, soaking in ethanol for 2 h, and finally replacing with deionized water, and avoiding light for 48 h to obtain a hydrogel.

[0094] Example

[0095] I. Preparation of the photo-switchable A3 molecule

[0096] Step one: mixing 2-methylbenzothiazole-6-amine (3 g) and triethylamine (2 g) in 30-50 mL dichloromethane, slowly adding methacryloyl chloride (2 g) dropwise under ice bath condition, and stirring overnight (6-8 h). After the reaction is completed, the mixture is poured into saturated NaHCO3 aqueous solution, extracted with dichloromethane, and dried with anhydrous sodium sulfate. After removing the solvent by rotary evaporation, column chromatography is performed with n-hexane / ethyl acetate (3:1) to purify and separate the white powder solid A1, with a yield of about 70%.

[0097] Step two, mix A1 molecules and 2-bromoethanol in a 1:3 molar ratio in an appropriate amount of acetonitrile, and react at 85-90°C. After 3 days, the reaction is complete. Remove a large amount of solvent by rotary evaporation, and then drop the solution into an ethyl ether solution to precipitate. Centrifuge and filter to obtain a light pink powder. Pour the powder into deionized water, wash with ethyl acetate, collect the aqueous phase, and remove water by rotary evaporation to obtain a light yellow powder A2, with a yield of about 70%.

[0098] Step three, mix A2 molecules, 1H-indazole-7-carboxaldehyde, and a small amount of polymerization inhibitor BHT and catalyst ammonium acetate NH4OAc in ethylene glycol, and react at 75-80°C. After 2 days, the reaction is complete. Remove a large amount of solvent by rotary evaporation, and then drop the solution into an ethanol solution to precipitate. Filter to collect the filter residue, wash the filter residue with tetrahydrofuran and acetone, centrifuge, filter, and then collect the orange yellow powder of the light switch A3 molecule. Dry and weigh to obtain a yield of about 60%.

[0099] II. Verification of the light response properties of the target molecule under neutral conditions

[0100] Test sample configuration:

[0101] Dissolve the light switch A3 molecule in deionized water to prepare a 0.05mM A3-DI water solution. Equilibrate overnight in the dark.

[0102] Test method: Take 2mL of the A3-DI water solution and add it to a four-way cuvette. Irradiate with blue light (450nm), and detect using an ultraviolet fiber optic spectrometer.

[0103] Test results: Under weak light intensity (5mW / cm 2 ), the absorption curve of the light switch A3 molecule in water solution changes from a solid line to a dashed line. The visible region absorption value decreases, and the ultraviolet region absorption value increases. As shown in the figure, the characteristic absorption peak of the sample at 409nm decreases from 0.9 (solid line-dark) before irradiation to about 0.1 (dashed line-light) after irradiation. Figure 2

[0104] Data analysis: ① The molecule can be characterized by relevant absorption values in a pure water system, proving that the synthesized molecule has certain water solubility. ② The molecule changes in ultraviolet absorption when irradiated with blue light in a pure water system, proving that the molecule has a blue light response behavior.

[0105] III. Test of the light response / dark recovery rate and kinetic curve of the target molecule under neutral conditions

[0106] Test results: Monitor the characteristic absorption peak of the sample at 409nm. Under weak light intensity (5mW / cm 2 ​Under the condition of irradiation for 90s in aqueous solution, the absorption value of the molecule decreases rapidly (the shaded area is the light irradiation period). After the light source is turned off, the absorption value gradually returns to the initial value. The light irradiation / dark recovery kinetics curve is as follows Figure 3 As shown in the figure, the change rate in the process is obtained by fitting the curve, as shown in the figure Figure 3 As shown in the figure, the absorption value of the characteristic peak before light irradiation is 0.9, and decreases to 0.2 after 15s of light irradiation. The absorption value returns to about 0.9 after 15min in the dark environment, the response speed is fast, and the recovery degree is high.

[0107] Data analysis: ①The molecule shows strong photosensitivity when tested in pure water system, and the fitting value of the light response rate is 0.091s -1 . ②Under dark environment / light shielding condition, the solution after light irradiation can quickly return to the original state. The fitting value of the recovery rate is 0.016s -1 .

[0108] Four, verify that the pKa of the target molecule meets the expectation

[0109] Test sample configuration:

[0110] The light switch A3 molecule is dissolved in a phosphate buffer (PB buffer) solution with different pH values, and the concentration of the A3 molecule is 0.05mM, and the salt concentration in the buffer is 20mM. The prepared A3-PB buffer solution is balanced in the dark overnight.

[0111] Test method: 2mL of A3 molecule solution with different pH values is added to two transmission cuvettes, and the absorption value of the characteristic peak at 409nm is detected by using an ultraviolet fiber spectrometer. The actual pH value after balancing overnight in the phosphate buffer solution with different pH values is recorded, and the absorption value of the characteristic peak at 409nm is recorded.

[0112] Data analysis: the absorption value of the A3-PB buffer solution at 409nm under different pH conditions is analyzed, as shown in the figure Figure 4 As shown in the figure, the absorption value of the 0.05mM A3-PB buffer solution under neutral conditions is about 0.8. The data is fitted by Boltzmann to obtain the pKa value of the light switch molecule A3, which is 7.66.

[0113] In summary, the pKa value of the light switch molecule A3 designed by the application is high (about 7.66), which can realize the stable ring opening and photoisomerization under neutral pH conditions, and meets the design expectation.

[0114] Five, preparation of a polymer material containing a light switch A3 molecule

[0115] Material preparation: The above-synthesized photoswitch A3 molecule, N-isopropyl acrylamide (NIPAM), N, N'-methylene bis-acrylamide (bis-MBA), ammonium persulfate (APS), tetramethyl ethylenediamine (TEMED), ascorbic acid (VC), N-methyl pyrrolidone (NMP), deionized water.

[0116] Configuration of aqueous solution of APS:

[0117] 150 mg of APS was added to 1 mL of water to configure a 15 wt% aqueous solution of APS.

[0118] Configuration of aqueous solution of VC:

[0119] 100 mg of VC was added to 1 mL of water to configure a 10 wt% aqueous solution of VC.

[0120] Configuration of mixed solvent:

[0121] NMP / water = 7:3 ~ 3:2 (w / w)

[0122] Preparation method: 100 ~ 150 mg of NIPAM and 7 ~ 11 mg of photoswitch A3 molecule were added to a 5 mL glass vial containing 900 μL of mixed solvent of NMP and water, and after ultrasonic dissolution, bis-MBA was added to mix uniformly. 100 μL of 15 wt% aqueous solution of APS was added to the above mixture, and Ar was introduced to remove oxygen, and after 3 min of oxygen removal, 30 μL of 10 wt% aqueous solution of VC was added dropwise in an ice bath.

[0123] After mixing uniformly, the prepolymer solution was injected into a certain thickness of interlayer glass mold for polymerization, and at room temperature, about 3 ~ 24 h for molding. After molding, the gel was taken out of the glass mold, soaked in ethanol for 2 h, and then replaced into deionized water, and after 48 h of light protection, the test was performed.

[0124] Six, polymer material containing polymerizable photoswitch A3 molecule realizes photo-induced shrinkage under neutral water condition

[0125] Test sample preparation: The above-prepared gel sample was cut into long strip-shaped samples of equal thickness, different length and width, and placed flat at the bottom of a glass container containing deionized water, or vertically suspended by wrapping with tin paper. The light was shone from the middle part of the long strip-shaped sample, and whether it produced macroscopic mechanical deformation after light irradiation was used to verify the response of the material to light irradiation.

[0126] Test conditions / lighting conditions: The test device is schematically shown in Figure 5 , wherein the light source used is a 450 nm blue light source conducted through an optical fiber, and the light intensity ranges from 1 ~ 3 mW / cm 2 .

[0127] Test results: as Figure 6 (left) shown, 0.5mm thick, 1mm wide, about 9cm long sample was wrapped with tin foil and hung vertically in deionized water, from the right side of the light, the gel showed a bending behavior to the light source (right side), after 2h of light, as Figure 6 (right) shown, the gel has a clear bending angle (~60°).

[0128] Result analysis: the prepared gel in deionized water when light, the light switch molecule A3 from ring to ring form, the material net charge occurs by +1→0 transition, the polymer chain becomes more hydrophobic, the gel side of the light gradually shrink, so that it macroscopically show bending to the light source (right side). Hydrogel material shows in neutral conditions occur photoinduced shrinkage of light responsive properties.

[0129] In summary, by virtue of the above technical scheme of the present application, by designing a high pKa (~7.66) of light switch A3 molecule, so that it remains in the ring form under the condition of neutral pH, overcomes the dependence on the preparation process of light responsive hydrogel and the recovery process after light on the acidic environment, so as to realize the application of light responsive hydrogel in neutral and physiological environment.

[0130] It should be understood that although each step in the flowchart of the accompanying drawings is shown in sequence according to the direction of the arrow, these steps are not necessarily executed in sequence according to the direction of the arrow. Unless otherwise specified herein, the execution of these steps is not strictly limited in sequence, and they can be executed in other orders. Moreover, at least part of the steps in the flowchart of the accompanying drawings can include multiple sub-steps or multiple stages, which are not necessarily executed at the same time, but can be executed at different times, and the execution sequence is not necessarily sequential, but can be alternately or alternately executed with at least part of other steps or other steps, sub-steps or stages.

Claims

1. A hydrogel which undergoes phototriggered shrinkage under neutral conditions, characterized in that, The hydrogel preparation raw material comprises the following components: The photo switch A3 molecule, N-isopropyl acrylamide, N, N'-methylene bisacrylamide and deionized water; The photo switch A3 molecule is an ionic compound, and the structure of the cationic part of the photo switch A3 molecule is shown in formula I:

2. A production method for producing the water gel which is subject to phototightening under neutral conditions according to claim 1, characterized by, The preparation method comprises: S1, preparing A1 molecule, the A1 molecule is N-(2-methylbenzothiazole-6-yl) methyl acrylamide; S2, based on A1 molecule, preparing A2 molecule, the A2 molecule is hydroxyethyl functionalized N-(2-methylbenzothiazole-6-yl) methyl acrylamide bromide; S3, based on A2 molecule, preparing photo switch A3 molecule; S4, based on photo switch A3 molecule, preparing hydrogel.

3. The method for preparing a hydrogel that undergoes photo-shrinkage under neutral conditions according to claim 2, characterized in that, The preparation of A1 molecule comprises: S11, mixing 2-methylbenzothiazole-6-amine and triethylamine in dichloromethane, and adding methyl acryloyl chloride drop by drop under ice bath condition, stirring for 6-8h to obtain a first mixture; S12, adding saturated NaHCO3 aqueous solution to the first mixture, extracting dichloromethane, and drying the first mixture with anhydrous sodium sulfate after extraction is completed; S13, removing residual solvent in the first mixture after drying by rotary evaporation, and purifying and separating the mixture by column chromatography to obtain A1 molecule in the form of white powder.

4. The method of claim 3, wherein the photo-shrinking of the hydrogel occurs at neutral conditions. The chemical formula of the preparation of A1 molecule is: wherein represents an A1 molecule; represents 2-methylbenzothiazol-6-amine; represents methacryloyl chloride; TEA represents triethylamine; DCM represents dichloromethane.

5. The method of claim 3, wherein the photo-shrinking of the hydrogel occurs at neutral conditions. The molar ratio of 2-methylbenzothiazole-6-amine, triethylamine and methyl acryloyl chloride is 1:1.2:1.2, and the eluent of n-hexane and ethyl acetate with a volume ratio of 3:1 is used for column purification to obtain the A1 molecule.

6. The method of claim 2, wherein the photo-shrinking of the hydrogel occurs at neutral conditions. The preparation of A2 molecule based on A1 molecule comprises: S21, mixing A1 molecule and 2-bromoethanol with a molar ratio of 1:3 in acetonitrile, and reacting at 85-90℃ for 3d to obtain a second mixture; S22, removing the solvent in the second mixture by rotary evaporation, and then adding dropwise into an ethyl ether solution for precipitation, and then centrifuging and filtering to obtain a light yellow powder; S23, pouring the light yellow powder into deionized water, washing with ethyl acetate, collecting the aqueous phase, and finally removing water by rotary evaporator to obtain A2 molecule in the form of light yellow powder.

7. The method of claim 6, wherein the hydrogel is prepared by the steps of: (a) dissolving the polymer of claim 1 in a solvent; (b) adding the solution of step (a) to a solution of a crosslinking agent; and (c) removing the solvent from the solution of step (b) to form the hydrogel. The chemical formula of the preparation of A2 molecule is: wherein represents the structure of the cationic part of the A2 molecule; represents an A1 molecule; represents 2-bromoethanol; CH3CN represents acetonitrile.

8. The method of claim 2, wherein the photo-shrinking of the hydrogel occurs at neutral conditions. The preparation of photo switch A3 molecule based on A2 molecule comprises: S31, mixing A2 molecule, 1H-indazole-7-formaldehyde, polymerization inhibitor BHT and catalyst ammonium acetate NH4OAc in ethylene glycol, and reacting at 75-80℃ for 2d to obtain a third mixture, wherein the molar ratio of A2 molecule, 1H-indazole-7-formaldehyde, polymerization inhibitor BHT and catalyst ammonium acetate NH4OAc is 1:1.5:0.1:0.2; S32, removing the solvent in the third mixture by rotary evaporation, then adding dropwise into an ethanol solution for precipitation, and then collecting the filter residue after filtration; S33, the filter residue is washed with tetrahydrofuran and acetone, and then centrifuged and filtered to collect the light switch A3 molecules in the form of orange yellow powder, and the light switch A3 molecules are weighed after drying.

9. The method for preparing a photo-shrinkable hydrogel under neutral conditions according to claim 8, characterized in that, The chemical formula of the preparation of the light switch A3 molecules is: wherein represents the structure of the cationic part of the photo-switch A3 molecule; represents the structure of the cationic part of the A2 molecule; represents 1 H-indazole-7-carbaldehyde; EG represents ethylene glycol.

10. The method of claim 2, wherein the photo-shrinking of the hydrogel occurs under neutral conditions. The preparation of the hydrogel based on the light switch A3 molecules comprises: S41, N-isopropyl acrylamide and light switch A3 molecules are added into a container containing a mixed solvent of N-methyl pyrrolidone and water, dissolved by ultrasonic, and then N, N'-methylene bisacrylamide is added and mixed uniformly to obtain a fourth mixture; S42, ammonium persulfate aqueous solution is added into the fourth mixture, and argon is introduced to remove oxygen, then ascorbic acid aqueous solution is added into the fourth mixture under ice bath condition, and mixed uniformly to obtain a prepolymer solution; S43, the prepolymer solution is injected into a laminated glass mold for polymerization, and the molded gel is obtained after being shaped at room temperature for 3-24 h, immersed in ethanol for 2 h, and finally replaced into deionized water, and the hydrogel is obtained after being kept in dark for 48 h.

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