Photoresponse molecule and preparation method thereof

Abstract

The photoresponse molecule comprises a chemical structure shown in a formula (I): # imgabs0 #, in the formula (I), L is CR, N, SiR'or # imgabs1 # R, R 'is any organic substituent group, X1, X2 and X3 are the same or different and are respectively and independently CH or N, and L1 is a direct bond, or is selected from at least one of a carbon atom, an alkyl group, an alkynyl group, a ketone group, a carboxyl group, an ester group, an aryl group and an amido group, or a substituted or unsubstituted arylene group.

Description

Technical Field

[0001] The present invention relates to the technical field of optical materials, and in particular to a photoresponsive molecule and a preparation method thereof. Background Art

[0002] "Photoresponsive molecules" are generally a type of organic molecules that can break intramolecular chemical bonds when exposed to light (generally high-energy ultraviolet light), effectively releasing the organic molecules or groups protected by them. This type of molecule was first used for the protection and deprotection of functional groups in organic synthesis. With further in-depth research, "photoresponsive molecules" have developed into an important means of light-regulated protein, gene, cell, and biological behavior. However, due to its increasingly widespread application, the limited types of existing "photoresponsive molecules" are often unable to adapt to new application scenarios, and more "photoresponsive molecules" with novel structures need to be developed to adapt to more application scenarios.

[0003] Hydrogel is a high molecular polymer with water as the main component and a three-dimensional network structure. It can be formed by physical or chemical cross-linking and has good hydrophilicity and biocompatibility. Therefore, it is widely used in many fields such as sensing, driving, drug delivery, wound dressing, etc. Therefore, from a macroscopic perspective, hydrogel material is a type of polymer skeleton with a high water retention capacity. It can maintain a three-dimensional network structure in the environment without dissolution, can withstand a certain external force, and can restore its original shape after the external force is removed, showing the viscoelasticity of a solid. From a microscopic perspective, due to the high water content inside the hydrogel, the polymer skeleton and water molecules in it penetrate each other without obvious boundaries. Small molecules can move and diffuse freely in it, and it also shows the properties of a liquid.

[0004] The high water content of traditional hydrogel molecules weakens the interaction between polymer chains and reduces the network cross-linking density, which makes the mechanical properties of traditional hydrogel molecules poor in the macroscopic sense. They are affected by the complex physiological environment in the body, such as ion concentration, pH value and protease, and cannot exist in the body for a long time. This limits the application of hydrogel molecules in the fields of tissue engineering and soft robots, because hydrogel molecules need to be greatly deformed or need to carry a large load when applied, such as to replace tendons and ligaments that carry weight in the body. Therefore, the mechanical properties of hydrogel molecules are very important for the application of hydrogel molecules. This field also needs to design new hydrogel molecule monomers to improve the physical, chemical, biological and other properties of hydrogel molecules. Summary of the invention

[0005] In view of the above-mentioned deficiencies in the prior art, the present invention designs the structure of the photoresponsive molecule (which can also be used as a hydrogel molecule) from a molecular level, by increasing the number of teeth of the photoresponsive molecule and adjusting the position of dissociation, so that under the action of light, the photoresponsive molecule produces active groups to initiate polymerization. As the number of teeth of the photoresponsive molecule increases, the more active groups dissociated are also more, which is equivalent to the higher local concentration of active groups participating in the reaction. In this way, at a certain temperature, the number of effective molecular collisions per unit time increases, the reaction rate is accelerated, the gelation time is shortened, and the gel efficiency is higher. In addition, the number of teeth of the photoresponsive molecule increases, and accordingly, the polymer chains connected thereto also increase accordingly. When decomposed by light, the number of polymer chains dissociated is also more. When entangled cross-linking occurs, the chain entanglement increases the rigidity of the hydrogel molecule, so that the formed three-dimensional network of the hydrogel will not be brittle, thereby improving the mechanical strength including rigidity and toughness.

[0006] Therefore, in the first aspect of the present invention, a photoresponsive molecule is provided, as shown in structural formula I:

[0007]

[0008] Wherein, in formula (I), L is CR, N, SiR′ or R and R' are arbitrary organic substituent groups. Preferably, R and R' are each independently selected from C1-C18 alkyl, C2-C18 alkenyl or C2-C18 alkynyl. More preferably, R and R' are each independently selected from C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl. More preferably, R and R' are each independently selected from C1-C4 alkyl.

[0009] X 1 , X 2 , X 3 are the same as or different from each other and are each independently CH or N,

[0010] L 1 is a direct bond, or a substituted or unsubstituted arylene group; preferably, L1 is a C6-C30 substituted or unsubstituted arylene group.

[0011] Furthermore, in formula (I), L 1 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 1 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group;

[0012] In formula (I), L is selected from a nitrogen atom, an alkyl group, a silane group, an aryl group, and a triazine;

[0013] In formula (I), The positions on the benzene ring are adjacent. It may be located at any substituent position on the benzene ring except L1.

[0014] Furthermore, the chemical structure of the photoresponsive molecule is shown in structural formula II:

[0015]

[0016] Among them, in formula (II), L 2 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 3 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 4 is selected from at least one of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 2 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 3 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 4 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group;

[0017] In formula (II), L is selected from a nitrogen atom, an alkyl group, a silane group, an aryl group, and a heteroaryl group; preferably, L is selected from a nitrogen atom, a C1-C18 alkyl group, a C1-C18 silane group, a C6-C18 aryl group, and a C6-C18 heteroaryl group.

[0018] Furthermore, L 2 , L 3 , L 4 Select one of the following structures:

[0019] Carbon atom, -CH 2 ,

[0020] Furthermore, L is selected from one of the following structures:

[0021] Nitrogen atom, -C-CH 3 、-Si-CH 3 ,

[0022] Furthermore, the chemical structure of the photoresponsive molecule is as follows:

[0023]

[0024]

[0025] Furthermore, the preparation method of the above-mentioned photoresponsive molecule includes esterification reaction, etherification reaction, Suzuki coupling reaction, and Sonogashira coupling reaction. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] For the convenience of describing the following examples, the chemical structures in this application are referred to in the following table:

[0028]

[0029]

[0030] In the present specification, unless specifically described to the contrary, a description that a part “includes” certain constituent elements means that other constituent elements can also be included, and other constituent elements are not excluded.

[0031] In this specification, the term "substituted" means that a hydrogen atom bonded to a carbon atom of a compound is changed into another substituent. The position of substitution is not limited as long as it is a position where a hydrogen atom is substituted, i.e., a position where a substituent can be substituted, and when two or more substituents are substituted, the two or more substituents may be the same or different from each other.

[0032] Throughout the specification of the present application, the term “combination thereof” included in a Markush-type expression means a mixture or combination of one or more selected from the constituent elements described in the Markush-type expression, and means including one or more selected from the constituent elements.

[0033] In the present specification, the alkyl group may be linear or branched, and although not particularly limited thereto, the number of carbon atoms is preferably 1 to 50. Specific examples thereof may include methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3 -dimethylcyclopentyl, cyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl, 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, cyclooctyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-propyl, isohexyl, 2-methylpentyl, 4-methylhexyl, 5-methylhexyl, etc., but are not limited thereto.

[0034] In the present specification, the alkynyl group may be linear or branched, and although not particularly limited thereto, the number of carbon atoms is preferably 2 to 30. Specific examples thereof may include ethynyl, propynyl, 2-methyl-2-propynyl, 2-butynyl, 2-pentynyl and the like, but are not limited thereto.

[0035] In the present specification, the aryl group is not particularly limited, but preferably has 6 to 60 carbon atoms, and may be a monocyclic aryl group or a polycyclic aryl group. According to one embodiment, the number of carbon atoms of the aryl group is 6 to 30. According to one embodiment, the number of carbon atoms of the aryl group is 6 to 20. When the aryl group is a monocyclic aryl group, examples thereof may include phenyl, biphenyl, terphenyl, etc., but are not limited thereto. Examples of polycyclic aryl groups may include naphthyl, anthracenyl, phenanthrenyl, pyrenyl, perylenyl, pyrenyl, fluorenyl, etc., but are not limited thereto.

[0036] In this specification, heteroaryl is a group containing one or more non-carbon atoms, i.e. heteroatoms, and specifically, heteroatoms can include one or more atoms selected from O, N, Si, Se, S, etc. The number of carbon atoms of heteroaryl is not particularly limited, but preferably 2 to 30, and heteroaryl can be monocyclic or polycyclic. The example of heteroaryl can include xanthene, thioxanthene, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, diazolyl, pyridyl, pyrimidyl, triazine, triazolyl, quinolyl, quinazolinyl, carbazolyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzocarbazolyl, benzothienyl, dibenzothienyl, benzofuranyl, phenanthroline, isoxazolyl, thiadiazolyl, dibenzofuranyl, etc., but is not limited thereto.

[0037] In the structural formulae in the present specification, Ph means a phenyl group, and Me means a methyl group.

[0038] The compound according to one embodiment of the present application can be prepared using a preparation method described later.

[0039] Hereinafter, this specification will be described in detail with reference to embodiments. However, embodiments according to this specification can be modified into various other forms, and the scope of this application should not be interpreted as being limited to the embodiments described below. The embodiments of this application are provided to more fully describe this specification to those of ordinary skill in the art.

[0040] Example 1 Preparation of Monomer 1

[0041] The preparation method of monomer 1 is as follows:

[0042]

[0043] First, triphenylethane is added to a 53% nitric acid solution to react to obtain structure 1, the compound of structure 1 is added to a carbon tetrachloride solution, AIBN (Azobisisobutyronitrile) and NBS (N-Bromosuccinimide) are added thereto, and the mixture is refluxed for 1.5 h under light conditions to obtain a compound of structure 2, the compound of structure 2 and thiourea are reacted in acetonitrile (ACN) at 40°C for 16 h, and then K is added. 2 CO 3 and Na 2 S 2 O 5 The mixed solution was reacted for 45 minutes, and then washed with DMF and water to separate the organic layer. The organic layer was purified by column chromatography to obtain a compound of structure 3, i.e., monomer 1, with a yield of 68%.

[0044] Comparative Example 1-1 (single tooth)

[0045] The synthesis method is shown in Example 1, and the synthesis route is as follows:

[0046]

[0047] Comparative Example 2-1 (double teeth)

[0048] The synthesis method is shown in Example 1, and the synthesis route is as follows:

[0049]

[0050] Example 2 Preparation of Monomer 2

[0051] The preparation method of monomer 2 is as follows:

[0052]

[0053] Compound C 8 H 8 BrNO 2 and C 6 H 9 B 3 O 6 Add to a mixed solution of acetone and water (volume ratio 3:1), and then add PdCl 2 and K 2 CO 3 , where the catalyst PdCl 2 The amount of the compound was 1.69 mol%, and the mixture was stirred at room temperature for 24 h to obtain a compound of structure 1 with a yield of 97%. Then, the compound of structure 1 in this example was added to a carbon tetrachloride solution, and AIBN (Azobisisobutyronitrile) and NBS (N-Bromosuccinimide) were added thereto, and the mixture was refluxed for 1.5 h under light conditions to obtain a compound of structure 2. The compound of structure 2 and thiourea were reacted in acetonitrile (ACN) at 40°C for 16 h, and then K was added. 2 CO 3 and Na 2 S 2 O 5 The mixed solution was reacted for 45 minutes, and then washed with DMF (dimethylformamide) to obtain a compound of structure 3, i.e., monomer 2, with a yield of 72%.

[0054] Comparative Example 1-2 (single tooth)

[0055] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0056] Comparative Example 2-2 (double teeth)

[0057] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0058] Example 3 Preparation of Monomer 3

[0059] The preparation method of monomer 3 is as follows:

[0060] 1,3,5-Benzenetricarboxylic acid chloride and 4-nitro-3-(trifluoromethyl)phenol were added to a mixed solvent of THF and pyridine, and the reaction was carried out at 0° C. for 18 h. The monomer 3 was purified and the yield was 89%.

[0061] Comparative Example 1-3 (single tooth)

[0062] The synthesis method is shown in Example 3, and the synthesis route is as follows:

[0063]

[0064] Comparative Example 2-3 (double teeth)

[0065] The synthesis method is shown in Example 3, and the synthesis route is as follows:

[0066]

[0067] Example 4 Preparation of Monomer 4

[0068] The preparation method of monomer 4 is as follows:

[0069]

[0070] 1,3,5-tribromotoluene, 5-hydroxy-2-nitrobenzoic acid methyl ester and K 2 CO 3 Add to DMF solution, react for 3h to obtain the intermediate product in the preparation method of this embodiment, and then react the intermediate product with Na 2 S 2 O 5 Reaction, in H 2 O and CH 2 Cl 2 The mixed solution was refluxed for 12 hours to obtain a crude product, which was then purified to obtain monomer 4.

[0071] Comparative Example 1-4 (single tooth)

[0072] The synthesis method is shown in Example 4, and the synthesis route is as follows:

[0073]

[0074] Comparative Example 2-4 (double teeth)

[0075] The synthesis method is shown in Example 4, and the synthesis route is as follows:

[0076]

[0077] Example 5 Preparation of Monomer 5

[0078] The preparation method of monomer 5 is as follows:

[0079]

[0080] 1,3,5-Triiodobenzene and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 5 with a yield of 67%.

[0081] Comparative Example 1-5 (single tooth)

[0082] The synthesis method is shown in Example 5, and the synthesis route is as follows:

[0083]

[0084] Comparative Example 2-5 (double teeth)

[0085] The synthesis method is shown in Example 5, and the synthesis route is as follows:

[0086]

[0087] Example 6 Preparation of Monomer 6

[0088] The preparation method of monomer 6 is as follows:

[0089]

[0090] 1,3,6-triethynylbenzene, C 7 H 6 BrNO 2 S and CuI (5 mol%) were added to a solvent of toluene and triethylamine, and then a catalyst PdCl was added thereto. 2 (PPh 3 ) 2 After reacting for 24 h, a crude product was obtained, which was purified to obtain monomer 6 with a yield of 92%.

[0091] Comparative Example 1-6 (single tooth)

[0092] The synthesis method is shown in Example 6, and the synthesis route is as follows:

[0093]

[0094] Comparative Example 2-6 (double teeth)

[0095] The synthesis method is shown in Example 6, and the synthesis route is as follows:

[0096]

[0097] Example 7 Preparation of Monomer 7

[0098] The preparation method of monomer 7 is as follows:

[0099]

[0100] 1,3,5-tribromobenzene, C 7 H 6 BrNO 2 S and K 2 CO 3 Introduce into a round-bottom flask and dissolve in methylpyrrolidone (NMP) (0.3 M), add CuI (5 mol%) and ferric acetylacetonate (10 mol%) under a nitrogen atmosphere, and stir at 150°C for 4 h. After the reaction, the reaction solution is cooled to room temperature, washed and purified by column chromatography to obtain monomer 7.

[0101] Comparative Example 1-7 (single tooth)

[0102] See Example 7 for the synthesis method. The synthesis route is as follows:

[0103]

[0104] Comparative Example 2-7 (double teeth)

[0105] See Example 7 for the synthesis method. The synthesis route is as follows:

[0106]

[0107] Example 8 Preparation of Monomer 8

[0108] The preparation method of monomer 8 is as follows:

[0109]

[0110] 1,3,5-aminobenzene and C 7 H 6 BrNO 2S and sodium tert-butoxide were introduced into the round-bottomed biscuit and dissolved in anhydrous toluene. Then, the mixed solution was stirred at room temperature for 10 min under a nitrogen atmosphere, and the oil container was heated from room temperature to 110°C. When the internal temperature became 60°C, 2,3-tert-butylphosphine palladium (9 mol%) was added dropwise thereto, and the resultant was stirred overnight. After the reaction, the obtained crude product was precipitated with CH 2 Cl 2 / H 2 O was washed and separated, and the monomer 8 was purified by column chromatography with a yield of 87%.

[0111] Comparative Example 1-8 (single tooth)

[0112] The synthesis method is shown in Example 8, and the synthesis route is as follows:

[0113]

[0114] Comparative Example 2-8 (double teeth)

[0115] The synthesis method is shown in Example 8, and the synthesis route is as follows:

[0116]

[0117] Example 9 Preparation of Monomer 9

[0118] The preparation method of monomer 9 is as follows:

[0119]

[0120] The synthesis method of monomer 9 can be found in Example 7. 10 H 15 F 3 , C 7 H 6 BrNO 2 S and K 2 CO 3 Introduce into a round-bottom flask and dissolve in methylpyrrolidone (NMP) (0.3M), add CuI (5 mol%) and ferric acetylacetonate (10 mol%) under a nitrogen atmosphere, and stir at 150°C for 4 hours. After the reaction, the reaction solution is cooled to room temperature, washed and purified by column chromatography to obtain monomer 9 with a yield of 94%.

[0121] Comparative Example 1-9 (single tooth)

[0122] See Example 9 for the synthesis method. The synthesis route is as follows:

[0123]

[0124] Comparative Example 2-9 (double teeth)

[0125] See Example 9 for the synthesis method. The synthesis route is as follows:

[0126]

[0127] Example 10 Preparation of Monomer 10

[0128] The preparation method of monomer 10 is as follows:

[0129]

[0130]

[0131] The preparation process of monomer 10 can be referred to Example 5, except that 1,3,5-triiodobenzene in Example 5 is replaced by C 18 H 12 I 3 N, specifically, C 18 H 12 I 3 N and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 10 with a yield of 71%.

[0132] Comparative Example 1-10 (single tooth)

[0133] See Example 10 for the synthesis method. The synthesis route is as follows:

[0134]

[0135] Comparative Example 2-10 (double teeth)

[0136] See Example 10 for the synthesis method. The synthesis route is as follows:

[0137]

[0138]

[0139] Example 11 Preparation of Monomer 11

[0140] The preparation method of monomer 11 is as follows:

[0141]

[0142] The preparation process of monomer 11 can refer to Example 5, except that the (3-methyl-4-nitrophenyl)boric acid in Example 5 is replaced by (2-nitrophenyl-3-methyl)boric acid. Specifically, 1,3,5-triiodobenzene and (2-nitrophenyl-3-methyl)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 11 with a yield of 69%.

[0143] Comparative Example 1-11 (single tooth)

[0144] The synthesis method is shown in Example 11, and the synthesis route is as follows:

[0145]

[0146] Comparative Example 2-11 (double teeth)

[0147] The synthesis method is shown in Example 11, and the synthesis route is as follows:

[0148]

[0149] Example 12 Preparation of Monomer 12

[0150] The preparation method of monomer 12 is as follows:

[0151]

[0152] The synthesis method of monomer 12 can refer to Example 5, except that 1,3,5-triiodobenzene is replaced by C 19 H 15I 3 Si, specifically, C 19 H 15 I 3 Si and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 12 with a yield of 68%.

[0153] Comparative Example 1-12 (single tooth)

[0154] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0155]

[0156] Comparative Example 2-12 (double teeth)

[0157] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0158]

[0159] Example 13 Preparation of Monomer 13

[0160] The preparation method of monomer 13 is as follows:

[0161]

[0162] The synthesis method of monomer 14 is similar to that of Example 5, except that 1,3,5-triiodobenzene is replaced by C 21 H 12 I 3 N 3 , specifically, C 21 H 12 I 3 N 3 and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2, react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 13 with a yield of 71.2%.

[0163] Comparative Example 1-13 (single tooth)

[0164] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0165]

[0166] Comparative Example 2-13 (double teeth)

[0167] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0168]

[0169] Example 14 Preparation of Monomer 14

[0170] The preparation method of monomer 14 is as follows:

[0171]

[0172]

[0173] The synthesis method of monomer 14 can refer to Example 5, except that (3-methyl-4-nitrophenyl)boric acid is replaced with (3-nitro-4-methyl)boric acid. Specifically, 1,3,5-triiodobenzene and (3-nitro-4-methyl)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5, reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 14 with a yield of 67%.

[0174] Comparative Example 1-14 (single tooth)

[0175] See Example 14 for the synthesis method. The synthesis route is as follows:

[0176]

[0177] Comparative Example 2-14 (double teeth)

[0178] See Example 14 for the synthesis method. The synthesis route is as follows:

[0179]

[0180] Example 15 Preparation of Monomer 15

[0181] The preparation method of monomer 15 is as follows:

[0182]

[0183] The synthesis method of monomer 15 can refer to Example 5, except that (3-methyl-4-nitrophenyl)boric acid is replaced by (2-methyl-3-nitro)boric acid. Specifically, 1,3,5-triiodobenzene and (2-methyl-3-nitro)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 15 with a yield of 68%.

[0184] Comparative Example 1-15 (single tooth)

[0185] See Example 15 for the synthesis method. The synthesis route is as follows:

[0186]

[0187] Comparative Example 2-15 (double teeth)

[0188] See Example 15 for the synthesis method. The synthesis route is as follows:

[0189]

[0190] Example 16 Preparation of hyaluronic acid molecules modified with photoresponsive molecules

[0191] Sodium hyaluronate is dissolved in deionized water to form a uniform, transparent solution, the photoresponsive molecules and 1-hydroxybenzotriazole synthesized in Example 1-Example 15 are dissolved in dimethyl sulfoxide respectively, and added dropwise in the reaction bottle, after the reaction mixture is stirred at room temperature for 5min, the pH value of the reaction solution is adjusted to 4.5, and now N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) is dissolved in dimethyl sulfoxide, and added dropwise to the reaction system. After the reaction mixture is stirred at room temperature for 48 hours, the reaction solution is loaded into a dialysis bag, and it is placed in a deionized water solution containing 0.1M NaCl with a pH of 3.5 and dialyzed for 2 days. Subsequently, it is placed in deionized water and continues to be dialyzed for 2 days, and the dialysate is changed every 3 hours during the dialysis process. After dialysis is completed, the mixed solution in the dialysis bag is placed in a 50mL centrifuge tube, and freeze-dried for 3 days under a dark state to collect white flocculent products.

[0192] The reaction formula of the preparation process is as follows:

[0193]

[0194] Comparative Example 3-1

[0195] The preparation method is the same as that of Example 16, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0196]

[0197] Comparative Example 4-1

[0198] The preparation method is the same as that of Example 16, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0199]

[0200] Example 17 Preparation of photoresponsive molecule-modified gelatin molecules

[0201] Add gelatin and CB buffer to a 250mL three-necked flask, heat at 50°C to dissolve and form a uniform transparent solution. Add the monomers prepared in Examples 1 to 15 dropwise to the reaction flask, and stir the reaction mixture at 50°C for 3 hours. After the reaction is completed, transfer the reaction mixture to a dialysis bag and dialyze in deionized water for 3 days. After dialysis, transfer the solution in the dialysis bag to a 50mL centrifuge tube and freeze-dry for 3 days in the dark to obtain a white foamy product.

[0202] The reaction formula of the preparation process is as follows:

[0203]

[0204] Comparative Example 3-2

[0205] The preparation method is the same as that of Example 17, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0206]

[0207] Comparative Example 4-2

[0208] The preparation method is the same as that of Example 17, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0209]

[0210] In the examples of the present application, not only are photoresponsive molecules and their corresponding hydrogel molecules prepared, comparative examples are constructed for verification, but also the prepared hydrogel molecules (tridentate) and the monodentate hydrogel molecules and bidentate hydrogel molecules of the comparative examples are tested, and the test method is as follows:

[0211] Rheological analysis: The rheological dynamics experiment was carried out under a UV light source (365 nm, 40 mW / cm 2 ) on a rheometer. Use a pipette to transfer 400 μL of the hydrogel precursor solution and spread it on the lower plate of the rheometer. A time scanning oscillation test was performed under ultraviolet light. Under controlled strain conditions, the oscillation amplitude was set to x, the test frequency was set to y, the plate spacing was set to 0.8 mm, and the test temperature was set to 25°C. The gel point was determined as the intersection of the storage modulus (G′) and the loss modulus (G″), and the final modulus was the average modulus when the storage modulus reached equilibrium.

[0212] It should be noted here that rheology mainly studies the phenomena of creep and stress relaxation of various materials, which are specifically manifested in changes in material viscosity and modulus. Storage modulus (G′): also known as the elastic modulus, refers to the amount of energy stored in the material due to elastic (reversible) deformation when the material is deformed, reflecting the elasticity of the material. Loss modulus (G″): also known as the viscous modulus, refers to the amount of energy lost due to viscous deformation (irreversible) when the material is deformed, reflecting the viscosity of the material. When G' is less than G”, the system mainly undergoes viscous deformation and the material is in liquid state; when G' is greater than G”, the system mainly undergoes elastic deformation and the material is in solid state; and when G' is equal to G”, the material is in a gel state, so the intersection of the G' and G” curves is defined as the gel point.

[0213] Mechanical property evaluation: When the compressive strain was 50%, the compressive strength of the hydrogels of the embodiments and comparative examples was tested. In addition, when a certain load was applied to the hydrogels of the embodiments and comparative examples under the condition of fixed strain, the corresponding stress during the loading and unloading process of the hydrogel was recorded.

[0214] Photocuring time: The in-situ gelation process of the hydrogel precursor solution prepared in the examples and comparative examples under ultraviolet light was tested, and the time from the start of light irradiation to the gelation of the hydrogel precursor solution was recorded. It should be noted that the gelation time generally refers to the time required for the gel solution to transform from a flowable liquid state to a gel state under a certain light.

[0215] There are two general definitions of gel time. One is the initial gel time, which is the time from when the hydrogel solution starts to crosslink until the gel system does not deform due to its own weight after inversion. The other is the stable gel time, which is the time required for the gel solution to be completely crosslinked. The macroscopic gel time is used here, which can be understood as the moment when the sol-gel transformation is observed macroscopically as the intermediate state of the whole process. At this time, the gel network has a certain strength but has not reached a stable state.

[0216] In order to facilitate the recording of the experimental performance obtained in the examples and comparative examples, the hydrogel molecules prepared in the examples, i.e., the tridentate hydrogel, are marked as TD-Gel (Tridentate Gel), the monodentate hydrogel in the comparative example is marked as MD-Gel (monodentate Gel), and the bidentate hydrogel in the comparative example is marked as BD-Gel (Bidentate Gel). The test results are shown in the following table:

[0217]

[0218]

[0219] The above experimental results prove that the mechanical properties and gel time of tridentate gel molecules are significantly improved compared with their corresponding bidentate gel molecules and monodentate gel molecules. The main reason is the effective dissipation of energy by the dynamic covalent cross-linking points dispersed inside the tridentate hydrogel. This dissipation process enables the hydrogel to maintain good recovery performance when subjected to large external mechanical forces, and still maintain structural integrity and high elasticity of the gel under large deformation.

[0220] The embodiment of the present invention also tests the photocuring performance of the photoresponsive molecules. The monomer 5 molecules obtained in Example 5 were dissolved in deionized water at a concentration of 6 wt % and a light power density of 40 mW / cm 2 It can be cured into gel within 5 minutes by irradiation with 365nm ultraviolet light.

Claims

1. A light-responsive molecule, It is characterized in that The photoresponsive molecule comprises a chemical structure of formula (I): Wherein, in formula (I), L is CR, N, SiR′ or R and R' are any organic substituent groups. Preferably, R and R' are each independently selected from C1-C18 alkyl, C2-C18 alkenyl or C2-C18 alkynyl. More preferably, R and R' are each independently selected from C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl. More preferably, R and R' are each independently selected from C1-C4 alkyl. X 1 , X 2 , X 3 are the same as or different from each other and are each independently CH or N, L1 is a direct bond, or at least one selected from a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aryl group, an amine group, or a substituted or unsubstituted arylene group; preferably, L1 is a C6-C30 substituted or unsubstituted arylene group.

2. A photoresponsive molecule according to claim 1, It is characterized in that In the formula (I), L 1 is selected from at least one of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 1 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; In the formula (I), L is selected from one of a nitrogen atom, an alkyl group, a silane group, an aryl group, and a triazine group; preferably, L is selected from one of a C1-C18 alkyl group, a C1-C18 silane group, and a C6-C18 aryl group; In the formula (I), The positions on the benzene ring are adjacent. It may be located at any substituent position on the benzene ring except L1.

3. A photoresponsive molecule according to claim 1, It is characterized in that The photoresponsive molecule has a structure as shown in formula (II): Among them, in formula (II), L 2 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 3 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 4 is selected from at least one of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 2 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 3 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 4 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; In formula (II), L is selected from a nitrogen atom, an alkyl group, a silane group, an aryl group, and a heteroaryl group; preferably, L is selected from a nitrogen atom, a C1-C18 alkyl group, a C1-C18 silane group, a C6-C18 aryl group, and a C6-C18 heteroaryl group.

4. A photoresponsive molecule according to claim 3, It is characterized in that The L 2 , L 3 , L 4 Select one of the following structures: Carbon atom, -CH 2 , 5. A photoresponsive molecule according to claim 3, It is characterized in that The L is selected from one of the following structures: Nitrogen atom, -C-CH 3 、-Si-CH 3 , 6. A photoresponsive molecule according to claim 3, It is characterized in that The chemical structure of the photoresponsive molecule is as follows:

7. A photoresponsive molecule according to claim 1, It is characterized in that The preparation method of the photoresponsive molecule includes esterification reaction, etherification reaction, Suzuki coupling reaction and Sonogashira coupling reaction.

8. The method according to claim 7, It is characterized in that The method is carried out along the following route: First, triphenylethane is added to a 53% nitric acid solution to react to obtain structure 1, the compound of structure 1 is added to a carbon tetrachloride solution, azobisisobutyronitrile and N-bromosuccinimide are added thereto, and refluxed under light conditions to obtain a compound of structure 2, the compound of structure 2 is reacted with thiourea in acetonitrile, and then K is added 2 CO 3 and Na 2 S 2 O 5 The mixed solution was reacted, and then washed with DMF and water to separate the organic layer, and purified by column chromatography to obtain a compound of structure 3, i.e., monomer 1.

9. The method according to claim 7, It is characterized in that The method is carried out along the following route: Compound C 8 H 8 BrNO 2 and C 6 H 9 B 3 O 6 Add to a mixed solution of acetone and water in a volume ratio of 3:1, and then add PdCl 2 and K 2 CO 3 The mixture is stirred at room temperature to obtain a compound of structure 1. Then, the compound of structure 1 is added to a carbon tetrachloride solution, to which azobisisobutyronitrile and N-bromosuccinimide are added, and refluxed under light conditions to obtain a compound of structure 2. The compound of structure 2 reacts with thiourea in acetonitrile, and then K is added. 2 CO 3 and Na 2 S 2 O 5 The mixture is reacted in a mixed solution and then washed with dimethylformamide to obtain a compound of structure 3, i.e., monomer 2.

10. The method according to claim 7, It is characterized in that The method is carried out along the following route: 1,3,5-Benzenetricarboxylic acid chloride and 4-nitro-3-(trifluoromethyl)phenol were added to a mixed solvent of THF and pyridine, and reacted at 0°C, and purified to obtain the monomer 3 compound.

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