CN106832324B - Preparation method of cucurbituril polymer with various topological structures - Google Patents

Abstract

The invention relates to a preparation method of cucurbituril polymers with various topological structures, which comprises the steps of oxidizing cucurbituril by persulfate to obtain monohydroxy cucurbituril and dihydroxy cucurbituril, further reacting in the presence of strong alkali sodium hydride to obtain mono alkynyl cucurbituril and diyne cucurbituril, and preparing the cucurbituril polymers with various topological structures by click reaction and azide-functionalized polymers with different structures. The polymer prepared by the method disclosed by the invention is regular in structure, rich in property and high in controllability, combines the advantages of cucurbituril in self-assembly, and has good application prospects in multiple fields of basic research, drug delivery, cell loading, functional material design, biochemical analysis and the like.

Description

Preparation method of cucurbituril polymer with various topological structures

technical field

The invention relates to a method for preparing a class of polymers, in particular to a method for preparing a class of polymers containing a cucurbituril structure, in particular to a method for preparing a cucurbituril end-capped polymer, a method for preparing a cucurbituril star polymer and a method for preparing a cucurbituril star-shaped polymer and a cucurbituril The invention relates to a preparation method of a main chain polymer, belonging to the technical field of organic synthesis.

Background technique

Cucurbituril is a macrocyclic host molecule composed of methylene bridged glycoluril units. According to the number of glycoluril units constituting its macrocycle, its family includes cucurbit[5]uril, cucurbit[6]uril, and cucurbit[7] ] urea, cucurbit[8] urea and cucurbit[10] urea. As a class of host molecules, it exhibits good structural selectivity and excellent binding strength with the corresponding guest molecules. In addition, cucurbituril has stable chemical structure, low biological toxicity and good biocompatibility. Literature research shows that cucurbituril has great application potential in many fields such as drug transportation and controlled release, analysis and detection, enrichment and separation, and construction of new functional materials. However, the extremely poor solubility and difficult functionalization of cucurbituril hinder its further application.

The construction of polymers containing cucurbituril structure not only provides a feasible method for overcoming the shortcomings of cucurbituril and exploiting the advantages of cucurbituril, but also further expands the application mode and scope of cucurbituril. For example: document Biomaterials, 2011, 32, 7687-7694 reported the method of cucurbituril grafting hyaluronic acid, document J.Polym.Sci., Part A:Polym.Chem., 2015,53,1748-1752 and Chinese patent Document CN104086691A discloses a preparation method of a polymer containing cucurbituril structure, and Chinese patent document CN103183743A discloses a preparation method of cucurbituril[6] (CB[6]) grafted chitosan. In addition, the literatures ACS Nano, 2012, 6, 2960-2968 and Scientific Reports, 2016, DOI: 10.1038/srep20722, etc. reported a method to further construct supramolecular hydrogels using polymers containing cucurbituril structure.

However, the polymers with cucurbituril structure reported at home and abroad are limited to two topological structures: side chain polymers and branched polymers. Therefore, it is of great significance to find a class of methods that can effectively prepare cucurbituril polymers with various topological structures.

SUMMARY OF THE INVENTION

In view of the deficiencies of the prior art, the present invention provides a method for effectively preparing cucurbituril polymers with various topological structures, including a method for preparing cucurbituril end-capped polymers, a method for preparing cucurbituril star-shaped polymers, and a method for preparing cucurbituril main polymers. Method for the preparation of chain polymers.

The cucurbituril end-capped polymer provided by the present invention is represented by formula (VII) and formula (IX), the cucurbituril star polymer is represented by formula (XI), and the cucurbituril main chain polymer is represented by formula (XII). .

The technical scheme of the present invention is as follows:

A kind of preparation method of the cucurbituril polymer with multiple topological structures, comprising the steps as follows:

(1) hydroxylation of cucurbituril represented by formula (I) to obtain a mixture containing monohydroxy cucurbituril represented by formula (II), dihydroxy cucurbituril represented by formula (III) and other polyhydroxy cucurbituril;

(2) separating and purifying a mixture containing monohydroxy cucurbituril represented by formula (II), dihydroxy cucurbituril represented by formula (III) and other polyhydroxy cucurbituril to obtain monohydroxy cucurbituril represented by formula (II) and Dihydroxycucurbituril represented by formula (III);

(3) reacting the monohydroxy cucurbituril represented by the formula (II) with bromopropyne under the action of sodium hydride to obtain the monoalkynyl cucurbituril represented by the formula (IV);

(4) reacting the dihydroxycucurbituril shown in formula (III) with bromopropyne under the action of sodium hydride to obtain the dialkynyl cucurbituril shown in formula (V);

(5) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the monoazide functionalized polymer represented by the formula (VI) to obtain the monocucurbituril end-capped polymer represented by the formula (VII); or,

(6) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the diazide functionalized polymer represented by the formula (VIII) to obtain the bicucurbituril-terminated polymer represented by the formula (IX); or,

(7) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the azide-functionalized star polymer represented by the formula (X) to obtain the cucurbituril star polymer represented by the formula (XI); or,

(8) reacting the dialkynyl cucurbituril represented by the formula (V) with the diazide functionalized polymer represented by the formula (VIII) to obtain the cucurbituril main chain polymer represented by the formula (XII);

Synthesis of Cucurbituril Terminated Polymer:

Synthesis of cucurbituril star polymer:

Synthesis of cucurbituril backbone polymer:

In the present invention, the chemical structure of cucurbituril shown in formula (I) is as follows:

According to the present invention, preferably, the process of cucurbituril hydroxylation in step (1) is as follows:

Disperse cucurbituril in water, add 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) dibromide to form a homogeneous solution; add persulfate to the obtained solution for oxidation Reaction to obtain a mixture containing formula (II), formula (III) and other polyhydroxy cucurbituril;

Preferably, the mass ratio of cucurbituril, 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) dibromide and persulfate is (0.1-2):(0.05 –1): (0.05–1); the ratio of the mass of cucurbituril to the volume of water is (0.1–2): (10–100) g/mL.

According to the present invention, preferably, the separation and purification process in step (2) is carried out in a chromatographic column; preferably, the filler in the chromatographic column is macroporous resin; more preferably, Mitsubishi Chemical CHP macroporous resin.

According to the present invention, preferably, in step (3), the mass ratio of monohydroxycucurbituril, sodium hydride and bromopropyne is (0.05-0.5): (0.05-0.2): (0.05-1); step (4) , the mass ratio of bishydroxycucurbituril, sodium hydride and bromopropyne is (0.05–0.5): (0.05–0.2): (0.05–1);

Preferably, the reactions in steps (3) and (4) are carried out in a strongly polar aprotic solvent, and further preferably, the strongly polar aprotic solvent is dimethyl sulfoxide or N,N '-dimethylformamide;

Preferably, the reaction products of step (3) and step (4) are obtained by precipitation, washing and purification with other solvents that are miscible with the reaction solvent; more preferably, methanol or acetone is used for precipitation, washing and purification.

According to the present invention, preferably, in steps (5), (6) and (7), the monoazide-functionalized polymer represented by formula (VI), the diazide-functionalized polymer represented by formula (VIII), and the formula (VIII) The azide-functionalized star polymer shown in (X) is a terminal azide-functionalized polyethylene glycol;

Further preferably, the monoazide-functionalized polymer represented by formula (VI) is α-azide-ω-methyl polyethylene glycol 2000 and α-azide-ω-methyl polyethylene glycol 4000.

Further preferably, the diazide-functionalized polymer represented by formula (VIII) is α,ω-azidopolyethylene glycol 2000 and α,ω-azidopolyethylene glycol 4000.

Further preferably, the azide-functionalized star polymer represented by formula (X) is azide-terminated four-arm polyethylene glycol 10000.

According to the present invention, preferably, in step (5), reaction process is as follows:

Disperse the monoalkynyl cucurbituril represented by the formula (IV) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the monoazide functionalized polymer represented by the formula (VI) to the solution, Add the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride as a catalyst for the reaction. After the reaction is completed, the chlorine is removed by dialysis. Potassium chloride and catalyzer, freeze-drying solution, obtains monocucurbituril end-capped polymer shown in formula (VII);

Preferably, the mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05g-0.2): (0.05-0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05g-0.2): (10–100) g/mL;

The added molar amount of the monoazide-functionalized polymer represented by the formula (VI) is 20%-100% of the molar amount of the monoalkynyl cucurbituril;

The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril.

According to the present invention, preferably, in step (6), reaction process is as follows:

Disperse the monoalkynyl cucurbituril represented by formula (IV) into water, add potassium chloride, filter out insolubles to obtain a clear solution; add the diazide functionalized polymer represented by formula (VIII) to the solution, The complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst for the reaction; after the reaction, the chlorine was removed by dialysis Potassium chloride and catalyzer, freeze-drying solution, obtain the polymer of bicucurbituril end-cap shown in formula (IX);

Preferably, the mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05g-0.2): (0.05-0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05g-0.2): (10–100) g/mL;

The added molar amount of the diazide-functionalized polymer represented by the formula (VIII) is 20%-100% of the molar amount of the monoalkynyl cucurbituril;

The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril.

According to the present invention, preferably, in step (7), reaction process is as follows:

Disperse the monoalkynyl cucurbituril represented by the formula (IV) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the azide-functionalized star polymer represented by the formula (X) to the solution , add the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride as a catalyst for the reaction; after the reaction, remove the Potassium chloride and catalyzer, freeze-dried solution, obtains the cucurbituril star polymer shown in formula (XI);

Preferably, the mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05g-0.2): (0.05-0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05g-0.2): (10–100) g/mL;

The added molar amount of the azide-functionalized star polymer represented by the formula (X) is 5%-25% of the molar amount of the monoalkynyl cucurbituril;

The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril.

According to the present invention, preferably, in step (8), reaction process is as follows:

Disperse the dialkynyl cucurbituril represented by the formula (V) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the diazide functionalized polymer represented by the formula (VIII) to the solution, The complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst for the reaction; after the reaction, the chlorine was removed by dialysis Potassium chloride and catalyzer, freeze-drying solution, obtains the cucurbituril main chain polymer shown in formula (XII);

Preferably, the mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05g-0.2): (0.05-0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05g-0.2): (10–100) g/mL;

The added molar amount of the diazide functionalized polymer represented by the formula (VIII) is 50%-150% of the molar amount of the dialkynyl cucurbituril;

The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril.

According to the present invention, preferably, the reactions described in step (5), step (6), step (7) and step (8) are carried out at 20-70°C.

According to the present invention, the preparation method of the cucurbituril polymer with multiple topological structures, a preferred embodiment is as follows:

(1) 0.1–2 g of the compound represented by formula (I), namely cucurbituril, is dispersed in 10–100 mL of ultrapure water, and 0.05–1 g of 3,3'-(1,8-dioctylene)-bis-(1 -ethylimidazole) dibromide to form a homogeneous solution; 0.05-1 g of persulfate is added to the obtained solution, and an oxidation reaction is carried out to obtain a mixture containing formula (II), formula (III) and other polyhydroxy cucurbituril;

(2) the above mixture is separated through a chromatographic column loaded with a macroporous resin to obtain monohydroxy cucurbituril and dihydroxy cucurbituril represented by formula (II) and formula (III);

(3) 0.05-0.5 g of the compound represented by the formula (II) reacts with 0.05-1 g of bromopropyne under the action of 0.05-0.2 g of sodium hydride to obtain the monoalkynyl cucurbituril represented by the formula (IV);

(4) 0.05-0.5 g of the compound represented by the formula (III), under the action of 0.1-0.3 g of sodium hydride, react with 0.1-1 g of bromopropyne to obtain the dialkynyl cucurbituril represented by the formula (IV);

(5) 0.05g-0.2g of the compound represented by formula (IV) is dispersed in water, 0.05-0.1g potassium chloride is added, and the insolubles are filtered off to obtain a clear solution; to the solution, the monolayer represented by formula (VI) is added Nitrogen-functionalized polymer, the molar amount of the monoazide-functionalized polymer is 20-100% of the compound represented by formula (IV); adding 2-20 mol% of the monoazide-functionalized polymer molar amount The complex of [1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was used as a catalyst for the reaction; after the reaction, potassium chloride was removed by dialysis And catalyzer, freeze-drying solution obtains the polymer of single cucurbituril modification shown in formula (VII);

(6) 0.05g-0.2g of the compound represented by formula (IV) is dispersed in water, 0.05-0.1g potassium chloride is added, and the insolubles are filtered off to obtain a clear solution; to the solution is added the bilayer represented by formula (VIII) Nitrogen-functionalized polymer, the molar amount of the diazide-functionalized polymer is 20-100% of the compound represented by formula (IV); the molar amount of the diazide-functionalized polymer added is 2-20 mol% of the triazole. The complex of [1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was used as a catalyst for the reaction; after the reaction, potassium chloride was removed by dialysis and catalyst, freeze-drying the solution to obtain the dicucurbituril modified polymer represented by formula (IX).

(7) 0.05g-0.2g of the compound represented by formula (IV) is dispersed in water, 0.05-0.1g potassium chloride is added, insoluble matter is filtered off to obtain a clear solution; azide represented by formula (X) is added to the solution Functionalized star-shaped polymer The molar amount of the azide-functionalized star-shaped polymer is 5-25% of the compound represented by the formula (IV); The complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was used as a catalyst for the reaction; after the reaction, the chloride was removed by dialysis Potassium and a catalyst, and the lyophilized solution obtains the cucurbituril-modified star polymer shown in formula (XI);

(8) Disperse 0.05g-0.2g of the compound represented by formula (V) into water, add 0.05-0.1g potassium chloride, filter out insoluble matter to obtain a clear solution; add the double stack represented by formula (VIII) to the solution Nitrogen-functionalized polymer, the molar amount of diazide-functionalized polymer is 50-150% of the compound represented by formula (V); adding tri[ The complex of 1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was used as a catalyst to react; after the reaction, potassium chloride and potassium chloride were removed by dialysis. catalyst, and freeze-drying the solution to obtain the cucurbituril main chain polymer represented by formula (XII).

In the above preparation method of the present invention, step (5), step (6), step (7) and step (8) use traditional catalysts, such as copper sulfate and sodium ascorbate catalysis, the effect is poor, and it is more difficult to purify.

The preparation method provided by the invention has the following advantages:

1. The preparation method of cucurbituril end-capped polymer, the preparation method of cucurbituril star polymer and the preparation of cucurbituril main chain polymer are realized for the first time.

2. The cucurbituril polymer is prepared by the click reaction, the conditions are mild, the reaction efficiency is high, and the side reactions are few. The reaction product has high yield and easy purification. The yield is as high as 70-95%.

3. By this method, biocompatible molecules can be derivatized, and then cucurbituril polymers with good biocompatibility can be synthesized.

4. The cucurbituril polymer synthesized by this method has a highly regular and controllable structure.

5. The introduction of cucurbituril into the polymer can give the polymer cucurbituril special functions, such as molecular recognition, etc. At the same time, the function and application range of cucurbituril can also be further expanded.

6. Compared with polymers containing other host molecules, polymers containing cucurbituril structure have stronger molecular recognition ability and better selectivity in aqueous phase.

Through the synthesis method of the present invention, a variety of cucurbituril polymers with different structures can be synthesized and prepared. Utilizing the excellent molecular recognition ability of cucurbituril, such polymers can be applied in many fields such as basic research, drug delivery, cell loading, functional material design, and biochemical analysis.

Description of drawings

Fig. 1 is the hydrogen nuclear magnetic resonance spectrum of the monohydroxy cucurbituril (take cucurbit[7]uril as an example) obtained in step (1) of Example 1 of the present invention.

Figure 2 is the mass spectrogram of the monohydroxy cucurbituril (take cucurbit[7]uril as an example) obtained in step (1) of Example 1 of the present invention (adding 3,3'-(1,8-dioctylidene)- Bis-(1-ethylimidazolium)dibromide as supporting guest molecule).

Fig. 3 is the hydrogen nuclear magnetic resonance spectrum of step (1) dihydroxycucurbituril (take cucurbit[7]uril as an example) in Example 1 of the present invention.

Fig. 4 is the mass spectrum of dihydroxycucurbituril (take cucurbit[7]uril as an example) obtained in step (1) of Example 1 of the present invention (adding 3,3'-(1,8-dioctylidene)- Bis-(1-ethylimidazolium)dibromide as supporting guest molecule).

Fig. 5 is the hydrogen nuclear magnetic resonance spectrum of the monoalkynyl cucurbituril (take cucurbit[7]uril as an example) obtained in step (2) of Example 1 of the present invention.

Figure 6 is the mass spectrogram of the monoalkynyl cucurbituril (take cucurbit[7]uril as an example) obtained in step (2) of Example 1 of the present invention (adding 3,3'-(1,8-dioctylene) - bis-(1-ethylimidazole) dibromide as supporting guest molecule).

Fig. 7 is the hydrogen nuclear magnetic resonance spectrum of the cucurbituril-terminated polymer obtained in step (3) of Example 1 of the present invention.

Fig. 8 is the hydrogen nuclear magnetic resonance spectrum of the dialkynyl cucurbituril (take cucurbit[7]uril as an example) obtained in step (2) of Example 5 of the present invention.

9 is the mass spectrogram of the dialkynyl cucurbituril (take cucurbit[7]uril as an example) obtained in step (2) of Example 5 of the present invention (adding 3,3'-(1,8-dioctylene) - bis-(1-ethylimidazole) dibromide as supporting guest molecule).

Fig. 10 is the hydrogen nuclear magnetic resonance spectrum of the cucurbituril main chain polymer obtained in step (3) of Example 5 of the present invention.

Figure 11 is the hydrogen nuclear magnetic resonance spectrum of the cucurbituril star polymer obtained in Example 7 of the present invention.

Detailed ways

The experimental methods used in the following examples are conventional methods unless otherwise specified.

The materials, reagents, etc. used in the following examples can be obtained from commercial sources unless otherwise specified.

Sodium hydride and ammonium persulfate in the following examples of the present invention were purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd.; bromopropyne, α-azide-ω-methyl polyethylene glycol 2000, α-azide-ω- Methyl polyethylene glycol 4000, α,ω-azide polyethylene glycol 2000, α,ω-azide polyethylene glycol 4000 and azide-terminated four-arm polyethylene glycol 10000 were purchased from Bailingwei Technology Co., Ltd.; Macroporous resin CHP2OP was purchased from Mitsubishi Chemical MCI; methanol, dimethyl sulfoxide and N,N'-dimethylformamide were purchased from Tianjin Fuyu Chemical Reagent Co., Ltd.; 3,3'-(1,8-diamidium Octyl)-bis-(1-ethylimidazole)dibromide was synthesized according to literature (Chem. Commun., 2012, 48, 3070-3072). Cucurbituril was synthesized according to literature (J. Org. Chem., 2001, 66, 8094-8100). Tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol was synthesized according to literature (Supramol. Chem., 2016, 28, 801-809).

Example 1

The preparation method of the double cucurbit[7] urea-terminated polymer, comprising the steps as follows:

(1) 1 g of cucurbit[7]uril and 0.3 g of 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) dibromide were dissolved in 80 mL of ultrapure water, and nitrogen was bubbled Degas for half an hour. Subsequently, 0.26 g of ammonium persulfate was added, and the reaction was carried out at 85° C. for 12 h. After the reaction, the solution was concentrated to about 10 mL by rotary evaporation, and separated by a chromatographic column packed with macroporous resin CHP 2OP to obtain the compound represented by formula (II) and 3,3'-(1,8-dioctylene) - 0.21 g of the complex of bis-(1-ethylimidazole) dibromide and the compound represented by formula (III) and 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) ) Dibromo complex 0.10 g.

(2) 0.2 g of the compound of formula (II) was dissolved in a mixed solution of 20 mL of dimethyl sulfoxide and 4 mL of N,N'-dimethylformamide, 0.1 g of sodium hydride was added at 0°C, and the reaction was carried out for 5 h. Subsequently, 1 mL of 80% toluene solution of bromopropyne was added, and the reaction was carried out overnight. After the reaction, the product was washed with methanol for three times to obtain 0.18 g of the monoalkynyl cucurbit[7]urea represented by formula (IV).

(3) Disperse 0.1 g of the compound represented by formula (IV) into water, add 0.05 g of potassium chloride, sonicate and stir, and filter out insoluble matter to obtain a clear solution. To this solution, 0.06 g of a monoazide-functionalized polymer represented by formula (VI) (α,ω-azide polyethylene glycol 2000 was used in this example) was added. A total of 5 mg of the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst, and the reaction was carried out at 50°C under nitrogen protection. 48h. After the reaction, the polymer was dialyzed and purified, and the solution was freeze-dried to obtain 0.10 g of the polymer with the end-capped dicucurbit[7]uril represented by the formula (IX). The yield was 70%.

Example 2

As described in Example 1, the difference is that in step (3), the polymer is α,ω-azide polyethylene glycol 4000, and the consumption of the polymer is 0.12g, and the double cucurbit [ 7] Urea terminated polymer 0.16 g. The yield was 84%.

Example 3

As described in Example 1, the difference is that in the step (3), the polymer is α-azide-ω-methyl polyethylene glycol 2000, and the amount of the polymer is 0.12 g, and the yield shown in formula (VII) Dicucurbit[7]uril-terminated polymer 0.14 g. The yield was 74%.

Example 4

As described in Example 1, the difference is that in the step (3), the polymer is α-azide-ω-methyl polyethylene glycol 4000, and the amount of the polymer is 0.24 g, and the yield shown in formula (VII) Dicucurbit[7]uril-terminated polymer 0.27 g. The yield was 84%.

Example 5

The preparation method of cucurbit[7] urea main chain polymer comprises the following steps:

(1) with step (1) in embodiment 1.

(2) 0.1 g of the compound of formula (III) was dissolved in a mixed solution of 10 mL of dimethyl sulfoxide and 2 mL of N,N'-dimethylformamide, 0.08 g of sodium hydride was added at 0°C, and the reaction was carried out for 5 h. Subsequently, 1 mL of 80% toluene solution of bromopropyne was added, and the reaction was carried out overnight. After the reaction, the methanol product was used for washing three times to obtain 0.10 g of dialkynyl cucurbit[7]urea represented by formula (V).

(3) Disperse 0.1 g of the compound represented by formula (V) into water, add 0.05 g of potassium chloride, sonicate and stir, and filter out insoluble matter to obtain a clear solution. To this solution, 0.08 g of a bisazide-functionalized polymer represented by formula (VIII) (α,ω-azide polyethylene glycol 2000 was used in this example) was added. A total of 5 mg of the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst, and the reaction was carried out at 50°C under nitrogen protection. 48h. After the reaction, the polymer was dialyzed and purified, and the solution was freeze-dried to obtain 0.12 g of the cucurbit[7]uril main chain polymer represented by the formula (XII). The yield was 90%.

Example 6

As described in Example 5, the difference is that in step (3), the polymer is α,ω-azide polyethylene glycol 4000, and the amount of the polymer is 0.16 g, and the cucurbit [7] shown in formula (XII) is obtained. ] urea backbone polymer 0.19g. The yield was 91%.

Example 7

The preparation method of cucurbit[7] urea star polymer comprises the following steps:

As described in Example 1, the difference is that the polymer in step (3) is azide-terminated four-arm polyethylene glycol 10000, and the amount of the polymer is 0.07 g, and the cucurbit[7] shown in formula (IX) is obtained. ] Urea star polymer 0.10 g. The yield was 91%.

Claims (10)

1. a preparation method of the cucurbituril polymer with multiple topological structures, comprising the steps as follows: (1) hydroxylation of cucurbituril represented by formula (I) to obtain a mixture containing monohydroxy cucurbituril represented by formula (II), dihydroxy cucurbituril represented by formula (III) and other polyhydroxy cucurbituril; (2) separating and purifying a mixture containing monohydroxy cucurbituril represented by formula (II), dihydroxy cucurbituril represented by formula (III) and other polyhydroxy cucurbituril to obtain monohydroxy cucurbituril represented by formula (II) and Dihydroxycucurbituril represented by formula (III); (3) reacting the monohydroxy cucurbituril represented by the formula (II) with bromopropyne under the action of sodium hydride to obtain the monoalkynyl cucurbituril represented by the formula (IV); (4) reacting the dihydroxycucurbituril shown in formula (III) with bromopropyne under the action of sodium hydride to obtain the dialkynyl cucurbituril shown in formula (V); (5) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the monoazide functionalized polymer represented by the formula (VI) to obtain the monocucurbituril end-capped polymer represented by the formula (VII); or, (6) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the diazide functionalized polymer represented by the formula (VIII) to obtain the bicucurbituril-terminated polymer represented by the formula (IX); or, (7) reacting the monoalkynyl cucurbituril represented by the formula (IV) with the azide-functionalized star polymer represented by the formula (X) to obtain the cucurbituril star polymer represented by the formula (XI); or, (8) reacting the dialkynyl cucurbituril represented by the formula (V) with the diazide functionalized polymer represented by the formula (VIII) to obtain the cucurbituril main chain polymer represented by the formula (XII); Monoazide-functionalized polymer represented by formula (VI), diazide-functionalized polymer represented by formula (VIII), and azide represented by formula (X) in steps (5), (6), (7) The functionalized star polymer is a terminal azide functionalized polyethylene glycol;

2. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (1), the process of cucurbituril hydroxylation is as follows: Disperse cucurbituril in water, add 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) dibromide to form a homogeneous solution; add persulfate to the obtained solution for oxidation Reaction to obtain a mixture containing formula (II), formula (III) and other polyhydroxy cucurbituril; The mass ratio of cucurbituril, 3,3'-(1,8-dioctylene)-bis-(1-ethylimidazole) dibromide and persulfate is (0.1–2): (0.05–1) : (0.05–1); the ratio of the mass of cucurbituril to the volume of water is (0.1–2): (10–100) g/mL. 3. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (2), separation and purification process is carried out in chromatographic column; The filler in chromatographic column is macroporous resin . 4. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (3), the mass ratio of monohydroxy cucurbituril, sodium hydride and bromopropyne is (0.05 – 0.5): (0.05 – 0.2): (0.05 – 1); In step (4), the mass ratio of bishydroxycucurbituril, sodium hydride and bromopropyne is (0.05-0.5): (0.05-0.2): (0.05-1); The reaction described in step (3) and step (4) is carried out in a strong polar aprotic solvent, and the strong polar aprotic solvent is dimethyl sulfoxide or N,N'-dimethylformamide ; The reaction products of step (3) and step (4) are obtained by precipitating, washing and purifying other solvents that are miscible with the reaction solvent. 5. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, The monoazide functionalized polymer represented by formula (VI) is α-azide-ω-methyl polyethylene glycol 2000, α-azide-ω-methyl polyethylene glycol 4000; The diazide-functionalized polymer represented by formula (VIII) is α,ω-azidopolyethylene glycol 2000, α,ω-azidopolyethylene glycol 4000; The azide-functionalized star polymer of formula (X) is azide-terminated four-arm polyethylene glycol 10000. 6. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (5), reaction process is as follows: Disperse the monoalkynyl cucurbituril represented by the formula (IV) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the monoazide functionalized polymer represented by the formula (VI) to the solution, Add the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride as a catalyst for the reaction. After the reaction is completed, the chlorine is removed by dialysis. Potassium chloride and catalyzer, freeze-drying solution, obtains monocucurbituril end-capped polymer shown in formula (VII); The mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05–0.2): (0.05–0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05–0.2): (10–100) g/mL; The added molar amount of the monoazide-functionalized polymer represented by the formula (VI) is 20%-100% of the molar amount of the monoalkynyl cucurbituril; The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril. 7. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (6), reaction process is as follows: Disperse the monoalkynyl cucurbituril represented by formula (IV) into water, add potassium chloride, filter out insolubles to obtain a clear solution; add the diazide functionalized polymer represented by formula (VIII) to the solution, The complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst for the reaction; after the reaction, the chlorine was removed by dialysis Potassium chloride and catalyzer, freeze-drying solution, obtain the polymer of bicucurbituril end-cap shown in formula (IX); The mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05–0.2): (0.05–0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05–0.2): (10–100) g/mL; The added molar amount of the diazide-functionalized polymer represented by the formula (VIII) is 20%-100% of the molar amount of the monoalkynyl cucurbituril; The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril. 8. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (7), reaction process is as follows: Disperse the monoalkynyl cucurbituril represented by the formula (IV) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the azide-functionalized star polymer represented by the formula (X) to the solution , add the complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride as a catalyst for the reaction; after the reaction, remove the Potassium chloride and catalyzer, freeze-dried solution, obtains the cucurbituril star polymer shown in formula (XI); The mass ratio of monoalkynyl cucurbituril to potassium chloride is (0.05–0.2): (0.05–0.1); the mass ratio of monoalkynyl cucurbituril to the volume of water is (0.05–0.2): (10–100) g/mL; The added molar amount of the azide-functionalized star polymer represented by the formula (X) is 5%-25% of the molar amount of the monoalkynyl cucurbituril; The added molar amount of the catalyst is 2%-20% of the molar amount of the monoalkynyl cucurbituril. 9. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, in step (8), reaction process is as follows: Disperse the dialkynyl cucurbituril represented by the formula (V) into water, add potassium chloride, filter out the insolubles to obtain a clear solution; add the diazide functionalized polymer represented by the formula (VIII) to the solution, The complex of tris[1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methanol and cuprous chloride was added as a catalyst for the reaction; after the reaction, the chlorine was removed by dialysis Potassium chloride and catalyzer, freeze-drying solution, obtains the cucurbituril main chain polymer shown in formula (XII); The mass ratio of dialkynyl cucurbituril to potassium chloride is (0.05–0.2): (0.05–0.1); the mass ratio of dialkynyl cucurbituril to the volume of water is (0.05–0.2): (10–100) g/mL; The added molar amount of the diazide functionalized polymer represented by the formula (VIII) is 50%-150% of the molar amount of the dialkynyl cucurbituril; The added molar amount of the catalyst is 2%-20% of the molar amount of the dialkynyl cucurbituril. 10. the preparation method of the cucurbituril polymer with multiple topology structures according to claim 1, is characterized in that, the reaction described in step (5), step (6), step (7) and step (8) Performed at 20–70°C.

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