[2+2] Method for preparing thermosensitive dendrimer microgels via photocycloaddition reaction

Abstract

The present invention discloses a method for preparing a thermosensitive dendritic macromolecule microgel by [2+2] photocycloaddition reaction, and relates to the field of intelligent microgels. First, an alkoxy ether dendritic macromolecule C3-TPA3 with temperature responsiveness is prepared by esterification reaction of alkoxy ether dendritic cinnamic acid and L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine, which exhibits characteristic temperature-sensitive behavior in the aqueous phase, i.e., thermally induced aggregation collapse. Subsequently, the three cinnamate sites of C3-TPA3 are subjected to [2+2] photocycloaddition reaction by in-situ ultraviolet irradiation, and the aggregates generated by temperature sensitivity are cross-linked and cured, thereby preparing a class of dendritic macromolecule microgels. The present invention prepares a class of dendritic macromolecule microgels by simple synthesis, which has important application value in the fields of intelligent materials, sensing and functional molecular envelopes.

Description

Technical Field

[0001] The invention relates to the technical field of smart microgels, in particular to a method for preparing thermosensitive dendritic macromolecular microgels through a [2+2] photocycloaddition reaction. Background Art

[0002] Stimuli-responsive microgels have unique micro-nano size, complete cross-linked network and intelligent response properties, and have important application value in the fields of drug carriers, sensors and biomolecule separation. At present, microgels are mainly prepared by precipitation polymerization of monomers or chemical cross-linking of polymers. Most of them are based on simple linear polymers, and stabilizers are often added during the preparation process. For example, Li et al. (W. Li, et al. Journal of Polymer Science Part A: Polymer Chemistry, 1999, 37 (15): 2899.) prepared a series of microgels by precipitation polymerization of divinylbenzene and different methacrylates, and proved the influence of comonomer polarity on microgel morphology. etc. (H. et al.ACS Applied Polymer Meter, 2022, 4(8): 5680.) explored the effects of cross-linker type and dosage, solvent composition, and the ratio of styrene monomers and maleic anhydride on the cross-linked microgels formed by precipitation copolymerization and their properties. In recent years, Zhang et al. (A. Zhang, et al. Chinese Journal of Polymer Science, 2020, 38: 1164.) used intermolecular cross-linking of dendrimers to prepare a new type of temperature-responsive OEG cationic dendritic copolymer nanogel, which exhibited high binding ability with siRNA at room temperature, but when triggered by ATP and heat-induced collapse at the same time, they can be effectively released. Despite this, most of the microgels reported so far are relatively complex to synthesize, require the additional introduction of stabilizers, etc., and have a single stimulus response. There are still many challenges in designing and preparing new multifunctional smart microgels. Summary of the invention

[0003] In order to solve the problems of the prior art, the present invention aims to overcome the shortcomings of the prior art and provide a method for preparing thermosensitive dendritic macromolecule microgels by [2+2] photocycloaddition reaction, and construct a class of dendritic macromolecules C by simple synthesis according to this method. 3 -TPA3, and on this basis, dendritic macromolecular microgels were prepared through [2+2] photocycloaddition reaction, which has important application value in the fields of smart materials, sensors and functional molecular envelopes.

[0004] One of the purposes of the present invention is to provide an alkoxy ether dendrimer, wherein the core of the alkoxy ether dendrimer is a triphenylamine unit, and the periphery is an alkoxy ether dendron unit and a cinnamate unit, and the structural formula of the alkoxy ether dendrimer is:

[0005]

[0006] Here, OEt represents ethoxy.

[0007] Preferably, the alkoxy ether dendron motif is temperature responsive and hydrophilic, the cinnamate motif is capable of undergoing a [2+2] photocycloaddition reaction, and the triphenylamine motif is hydrophobic.

[0008] The second object of the present invention is to provide a method for preparing an alkoxy ether dendrimer, comprising the following three steps:

[0009] Dissolve L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine, alkoxy ether dendronized cinnamic acid, DMAP and EDC HCl in a third portion of dry DMF, ice bath for 0.5 h, then terminate the ice bath, and place in a nitrogen atmosphere for reaction until the reaction is completed to obtain a third mixture, and sequentially perform concentration and column chromatography purification on the third mixture to obtain an alkoxy ether dendron macromolecule;

[0010] The structural formula of the L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine is:

[0011]

[0012] The structural formula of alkoxy ether dendronized cinnamic acid is:

[0013] Preferably, the synthesis method of the L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine is as follows: dissolving the 4,4,4-tricarboxylic acid triphenylamine active ester in a second portion of dry DMF, removing oxygen, and then dropwise adding L-propylamino alcohol at -15°C until the reaction is completed to obtain a second mixture, and sequentially performing two steps of concentration and column chromatography purification on the second mixture to obtain L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine;

[0014] The structural formula of the 4,4,4-tricarboxylic acid triphenylamine active ester is:

[0015]

[0016] Preferably, the synthesis method of the 4,4,4-tricarboxylic acid triphenylamine active ester is: dissolving 4,4,4-tricarboxylic acid triphenylamine and NHS in a first portion of dried DMF, adding EDC HCl to obtain a first mixed solution, placing the first mixed solution in an ice bath for 0.5 h, ending the ice bath, and reacting under a nitrogen atmosphere to obtain a first mixture after the reaction is completed, concentrating and extracting the first mixture in sequence to obtain a crude product, and then subjecting the first mixture to column chromatography purification to obtain the product 4,4,4-tricarboxylic acid triphenylamine active ester.

[0017] Preferably, the completion of the reaction is determined by detection on a TLC plate.

[0018] Preferably, the temperature during the reaction under the protection of nitrogen atmosphere is 30°C.

[0019] The third object of the present invention is to provide a method for preparing an alkoxy ether dendrimer microgel, comprising the following three steps:

[0020] The alkoxy ether dendritic macromolecule prepared by the preparation method of the alkoxy ether dendritic macromolecule is mixed with pure water to form an aqueous solution, the aqueous solution is heated to a reaction temperature T to obtain a thermosensitive aggregate, and then the thermosensitive aggregate is in situ irradiated with ultraviolet light to obtain a dendritic macromolecule microgel.

[0021] Preferably, the reaction temperature T is greater than 27°C.

[0022] Preferably, the parameters of the ultraviolet light in-situ irradiation are: the ultraviolet light wavelength is 365nm, and the irradiation time is 5min.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The present invention provides a method for preparing dendritic macromolecules and dendritic macromolecule microgels, 3 -TPA3 exhibits characteristic temperature-sensitive behavior in the aqueous phase, namely, thermally induced aggregation collapse; in situ ultraviolet irradiation enables C 3 -TPA3's three cinnamate sites undergo a [2+2] photocycloaddition reaction, and the temperature-sensitive aggregates are cross-linked and solidified, thereby preparing a type of dendritic macromolecular microgel. It can be seen that this method can prepare microgels using only the [2+2] photocycloaddition reaction, and the preparation conditions are mild and simple with a high yield.

[0025] The dendrimer prepared by the present invention is based on the thermosensitive behavior of the minimum co-solubility temperature of alkoxy ethers, C 3 -TPA3 also exhibited temperature-responsive behavior.

[0026] The structure of the dendritic macromolecular microgel prepared by the present invention is introduced with alkoxy ether to achieve the stimulation responsiveness of the microgel. The size of the microgel can be regulated between 120 and 230 nm by the solution temperature and concentration. Based on the LCST temperature-sensitive behavior of the alkoxy ether, the dendritic macromolecular microgel also exhibits temperature-responsive behavior.

[0027] The dendritic macromolecular microgel prepared by the present invention has important application value in the fields of smart materials, sensors and functional molecular envelopes. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The dendrimer C prepared in the present invention 3 - Turbidity curve of TPA3 solution with a mass fraction of 1 wt%;

[0029] Figure 2 is the UV-visible spectrum of MG1-30 of Example 1 of the present invention;

[0030] Figure 3 The figure is the morphology of MG1-30 of Example 1 of the present invention, and the inset is the particle size distribution diagram of MG1-30;

[0031] Figure 4 is the particle size of MG1-30, MG1-50 and MG2-30 in the present invention;

[0032] Figure 5 The particle sizes of MG1-30, MG1-50 and MG2-30 in the present invention vary with temperature. DETAILED DESCRIPTION

[0033] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. 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.

[0034] For ease of understanding, the English nouns or abbreviations mentioned below are first explained:

[0035] TPA-COOH: 4,4,4-Triphenylamine tricarboxylate

[0036] NHS: N-hydroxysuccinimide;

[0037] DMF: N,N-dimethylformamide;

[0038] EDC HCl: 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride;

[0039] DMAP: 4-dimethylaminopyridine;

[0040] The structural formula of alkoxy ether dendronized cinnamic acid is:

[0041] LCST: Lower critical phase transition temperature, abbreviated as T cp ;

[0042] AFM: atomic force microscope;

[0043] TLC plate: also known as climbing plate, the full name is thin layer chromatography;

[0044] Temperature: temperature;

[0045] Transmittance: transmittance;

[0046] Heating: heating process;

[0047] Cooling: cooling process;

[0048] Wavelength: wavelength;

[0049] Absorbance: Absorption;

[0050] Supematant: supernatant;

[0051] Redispersion: dispersion;

[0052] Diameter: diameter;

[0053] Count: count;

[0054] Radius: radius;

[0055] R h : hydrodynamic radius;

[0056] f(R h ):distributed.

[0057] The present invention provides the following technical solution: A method for preparing a thermosensitive dendritic macromolecular microgel by [2+2] photocycloaddition reaction, comprising the following steps:

[0058] S1. Synthesize 4,4,4-tricarboxylic acid triphenylamine active ester TPA-Su, specifically:

[0059] TPA-COOH (0.79 mmol) and NHS (3.5 mmol) were dissolved in dry DMF (15 mL), and EDC HCl (3.5 mmol) was added to obtain a first mixed solution. The first mixed solution was placed in an ice bath for 0.5 h, and then the ice bath was terminated. The mixture was placed in a nitrogen atmosphere for reaction until the reaction was completed to obtain a first mixture. The first mixture was concentrated and extracted in sequence to obtain a crude product, and then purified by column chromatography to obtain a product, 4,4,4-tricarboxylic acid triphenylamine active ester, which was labeled as TPA-Su. The structural formula of TPA-Su is:

[0060]

[0061] S2. Synthesis of L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine TPA-L, specifically:

[0062] TPA-Su (0.3 mmol) was dissolved in dry DMF (15 mL), and L-propanol (1.2 mmol) was added dropwise at -15°C after oxygen was removed. After the reaction was completed, a second mixture was obtained. The second mixture was concentrated and purified by column chromatography in two steps to obtain L-propanol-modified 4,4,4-tricarboxylic acid triphenylamine, which was marked as TPA-L. The structural formula of TPA-L is:

[0063]

[0064] S3. Synthesis of dendrimer C 3 -TPA3, specifically:

[0065] TPA-L (0.18 mmol), alkoxyether dendronized cinnamic acid (0.65 mmol), DMAP (0.65 mmol) and EDCHCl (0.65 mmol) were dissolved in 15 mL of dry DMF, and the mixture was placed in an ice bath for 0.5 h, and then the ice bath was terminated. The mixture was placed in a nitrogen atmosphere for reaction until the reaction was completed, and a third mixture was obtained. The third mixture was sequentially concentrated and purified by column chromatography to obtain a dendrimer, which was labeled as: C 3 -TPA3, C 3 The structural formula of -TPA3 is:

[0066]

[0067] Wherein, OEt represents ethoxy;

[0068] S4. Synthesize microgel MGe-T, specifically:

[0069] C 3-TPA3 is used to prepare an aqueous solution with a concentration of e (in mg / mL), which is heated to a reaction temperature T (in °C) to obtain a thermosensitive aggregate, and then the thermosensitive aggregate is irradiated in situ by ultraviolet light to obtain a dendritic macromolecular microgel, which is labeled as: MGe-T.

[0070] Furthermore, the temperature during the reaction under the protection of the nitrogen atmosphere is 30°C.

[0071] Furthermore, the completion of the above reaction is determined by detection via TLC plate.

[0072] Furthermore, the reaction temperature T is greater than C 3 -LCST of TPA3.

[0073] Dendrimer Temperature Sensitivity Test: Dendrimer C 3 -TPA3 has an obvious amphiphilic structure and can be well dissolved in water at low temperatures. When the aqueous solution is heated to a certain temperature, the aqueous solution begins to become turbid, which is called LCST, and thermosensitive aggregates are formed. The specific LCST test is: take 3 mg of C with a concentration of e = 1 mg / mL 3 -TPA3 pure aqueous solution, after being dissolved evenly, the phase change process was tracked by variable temperature UV / vis. The results are shown in Figure 1 At this concentration, the LCST of the dendrimer is 27°C.

[0074] Furthermore, the parameters of the ultraviolet light in-situ irradiation are: the ultraviolet light wavelength is 365nm, and the irradiation time is 5min.

[0075] Specifically, by C 3 The principle of obtaining thermosensitive aggregates by reacting with -TPA3 and then obtaining microgels by reacting is as follows:

[0076]

[0077] The difference between Examples 1 to 3 is the difference in e and T, specifically:

[0078] Embodiment 1:

[0079] The value of e is 1 mg / mL, the value of T is 30°C, and the finally prepared microgel is labeled as: MG1-30.

[0080] Embodiment 2:

[0081] The value of e is 1 mg / mL, the value of T is 50°C, and the finally prepared microgel is labeled: MG1-50.

[0082] Embodiment 3:

[0083] The value of e is 2 mg / mL, the value of T is 30°C, and the finally prepared microgel is labeled as: MG2-30.

[0084] The following is an introduction to the tests of the microgels prepared in Examples 1 to 3:

[0085] 1. UV-Visible Light Test

[0086] MG1-30 was centrifuged and washed with water to obtain washed microgels, and the washed microgels were redispersed in water to obtain a dispersion. 3 -TPA3, supernatant and redispersion after centrifugation were tested by UV-visible light. The results are as follows Figure 2 As shown in the figure: the absorption peak of cinnamate at 310nm in the UV absorption spectrum of the dispersion almost disappears, leaving only the absorption peak of the core triphenylamine, indicating that C 3 -TPA3 efficiently underwent [2+2] photocycloaddition cross-linking reaction at the aggregate scale to generate microgels.

[0087] It should be noted that the washed gel is dispersed again in water to prepare a dispersion. The specific method is as follows: the amount of the supernatant after centrifugation of MG1-30 is the amount of pure water added during the redispersion. In addition, the dispersion is also a microgel, called a dispersed microgel.

[0088] 2. AFM test

[0089] The MG1-30 dispersion was drop-coated on a mica substrate, and the size and morphology of the dispersed microgels were observed by AFM. Figure 3 As shown, the dispersed microgels spread on the mica substrate in a uniform spherical state with a narrow dispersion.

[0090] 3. Variable temperature dynamic light scattering test

[0091] The microgels prepared in Examples 1 to 3 were subjected to temperature-dependent dynamic light scattering tests, and all microgels underwent thermal shrinkage at the single particle level, retaining the temperature-sensitive behavior characteristics of the alkoxy ether dendrimers. Specifically, Figure 4 As shown in the distribution curves of the particle sizes of MG1-30, MG1-50 and MG2-30 at 20°C, it can be seen that at this time, the R h 198nm, MG1-50 R h 142nm, MG2-30 R h is 226nm. Figure 5 As shown in Figure 2, when the temperature increases from 20℃ to 50℃, MG2-30 shrinks significantly, and its R hThe R of the smaller MG1-50 has dropped significantly from 226nm to 172nm. h The molecular weight of MG1-30 can be reduced from 198nm at 20℃ to 161nm at 50℃.

[0092] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is limited by the attached embodiments and their equivalents.

Claims

1. A dendrimer, characterized in that The core of the dendritic macromolecule is triphenylamine moiety, and the periphery is alkoxy ether dendron moiety and cinnamate moiety. The structural formula of the dendritic macromolecule is: Here, OEt represents ethoxy.

2. The dendrimer according to claim 1, characterized in that The alkoxy ether dendron unit is temperature responsive and hydrophilic, the cinnamate unit has the ability to undergo a [2+2] photocycloaddition reaction, and the triphenylamine unit is hydrophobic.

3. A method for preparing an alkoxy ether dendrimer, characterized in that: The alkoxy ether dendrimer is the dendrimer according to any one of claims 1 to 2, and the preparation method is to dissolve L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine, alkoxy ether dendrimer cinnamic acid, DMAP and EDC HCl in a third portion of dry DMF, ice bath for 0.5 hours, end the ice bath, and react under nitrogen atmosphere protection until the reaction is completed to obtain a third mixture, and sequentially concentrate and purify the third mixture by column chromatography to obtain the alkoxy ether dendrimer; The structural formula of the L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine is: The structural formula of alkoxy ether dendronized cinnamic acid is:

4. The method for preparing the alkoxy ether dendrimer according to claim 3, characterized in that: The synthesis method of the L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine is as follows: dissolving the 4,4,4-tricarboxylic acid triphenylamine active ester in a second portion of dry DMF, removing oxygen, and then dropwise adding L-propylamino alcohol at -15°C until the reaction is completed to obtain a second mixture, and sequentially performing two steps of concentration and column chromatography purification on the second mixture to obtain the L-propylamino alcohol-modified 4,4,4-tricarboxylic acid triphenylamine; The structural formula of the 4,4,4-tricarboxylic acid triphenylamine active ester is:

5. The method for preparing the alkoxy ether dendrimer according to claim 4, characterized in that: The synthesis method of the 4,4,4-tricarboxylic acid triphenylamine active ester comprises: dissolving 4,4,4-tricarboxylic acid triphenylamine and NHS in a first portion of dried DMF, adding EDC HCl to obtain a first mixed solution, placing the first mixed solution in an ice bath for 0.5 hours, ending the ice bath, placing the first mixed solution in a nitrogen atmosphere for reaction, and obtaining a first mixture after the reaction is completed, concentrating and extracting the first mixture in sequence to obtain a crude product, and then subjecting the first mixture to column chromatography purification to obtain a product, 4,4,4-tricarboxylic acid triphenylamine active ester.

6. The method for preparing the alkoxy ether dendrimer according to any one of claims 3 to 5, characterized in that: The completion of the reaction was determined by detection on a TLC plate.

7. The method for preparing the alkoxy ether dendrimer according to claim 6, characterized in that: The temperature during the reaction under the protection of nitrogen atmosphere is 30°C.

8. A method for preparing an alkoxy ether dendrimer microgel, characterized in that: The alkoxy ether dendrimer and pure water are mixed into an aqueous solution, the aqueous solution is heated to a reaction temperature T to obtain a thermosensitive aggregate, and then the thermosensitive aggregate is in situ irradiated with ultraviolet light to obtain a dendrimer microgel.

9. The method for preparing the alkoxy ether dendrimer microgel according to claim 8, characterized in that: The reaction temperature T is greater than 27°C.

10. The method for preparing the alkoxy ether dendrimer microgel according to claim 8, characterized in that: The parameters of the ultraviolet light in-situ irradiation are: the ultraviolet light wavelength is 365nm, and the irradiation time is 5min.

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