CN114479044B - Preparation and application of biodegradable functional hyperbranched polycarbonate compound - Google Patents

Abstract

The invention discloses the preparation and application of a biodegradable functional hyperbranched polycarbonate compound. The functional hyperbranched polycarbonate is obtained by reacting a cyclic carbonate monomer and a mercapto alcohol compound to obtain a hydroxylated cyclic carbonate, and then ring-opening polymerization with a cyclic carbonate with a functional group Functional hyperbranched polycarbonate. The present invention quickly and easily obtains functionalized polycarbonate through a one-pot method, has high drug loading rate, highly branched three-dimensional topological structure, good biocompatibility, simple synthetic route, and is a kind of more convenient development, A more efficient method for preparing functional polycarbonates.

Description

Preparation and application of biodegradable functional hyperbranched polycarbonate compound

technical field

The invention relates to a preparation method and application of a polymer material, in particular to a preparation method and application of a biodegradable functional hyperbranched polycarbonate compound.

Background technique

Hyperbranched polymers (HBPs), a type of highly branched three-dimensional network molecules, have received extensive attention in the past few decades. This new type of hyperbranched polymer has been widely used in drug delivery due to its highly branched three-dimensional topology with many excellent properties such as monodispersity, multiple reaction sites at the periphery, controllable size, and good repeatability. field. However, the preparation of hyperbranched polymers requires tedious multi-step synthesis steps, and common hyperbranched polymer carriers such as hyperbranched polyethyleneimine, hyperbranched polyamidoamine, etc., generally have high cytotoxicity and biodegradability. shortcoming.

In order to overcome the above shortcomings, more and more researchers are devoting themselves to the development and design of biodegradable hyperbranched polymers. In addition, the functionalization of polymers is also an important aspect, which is of great significance for subsequent chemical modification of polymers and meeting the multifunctional requirements of drug carriers. For example, Chen Xuesi et al. synthesized lactide and carbonate copolymer microspheres containing alkyne groups. The surface "Click" reaction of the microspheres with azide-modified bovine serum albumin resulted in the polymerization of BSA grafted on the surface. object microspheres. However, the synthesis of functional polycarbonates always involves the protection and deprotection of functional groups, resulting in complex synthetic routes and low yields. Therefore, developing more convenient and efficient methods to prepare functional polycarbonates is still an active research area.

Contents of the invention

Purpose of the invention: the purpose of this invention is to provide a kind of preparation method of biodegradable functional hyperbranched polycarbonate.

Technical solution: The present invention generates hydroxylated cyclic carbonates by reacting cyclic carbonate monomers with mercapto alcohols, and then ring-opening polymerizes with cyclic carbonates with functional groups to obtain functionalized hyperbranched polymers. Carbonate.

Further, the cyclic carbonate monomer is selected from compounds with the following structures:

其中，R₁选自H或者CH₃，R₂选自N₃、炔基、ONO₂、Br等。

Wherein, R ₁ is selected from H or CH ₃ , and R ₂ is selected from N ₃ , alkynyl, ONO ₂ , Br and the like.

Further, the mercapto alcohol compound is selected from compounds with the following structures:

其中，R₃选自C2-C4烷基或C4-C8芳基。

Wherein, R ₃ is selected from C2-C4 alkyl or C4-C8 aryl.

Further, the ring-opening polymerization catalyst is selected from: 1,8-diazabicycloundec-7-ene (DBU), stannous octoate (Sn(Oct) ₂ ), 4-dimethylaminopyridine (DMAP) or zinc bis(bistrimethylsilyl)amine (Zinc).

The preparation method of the described biodegradable functional hyperbranched polycarbonate, taking preferred process conditions as an example, comprises the following steps:

(1) Cyclic carbonate monomers and a certain proportion of mercapto alcohol compounds are reacted for 2-6 hours with dichloromethane as a solvent to obtain intermediate product hydroxylated cyclic carbonates.

(2) Continue to add cyclic carbonates and catalysts with other functional groups in the reaction mixture to initiate ring-opening polymerization, and react to obtain functional hyperbranched polycarbonate.

Beneficial effect: compared with the prior art, the present invention has the following advantages:

The synthesis of the hyperbranched polycarbonate can be directly synthesized by a one-pot method to obtain the hyperbranched polycarbonate with functional groups. The synthesis process is simple and convenient, and the drug loading rate is high. Biocompatibility, the metabolites are harmless to the human body. This functionalized polycarbonate can further undergo corresponding chemical reactions with other compounds with functional groups, making it have great application prospects in drug delivery and tumor treatment.

Description of drawings

Fig. 1 is the proton nuclear magnetic spectrum of azide polycarbonate ( ^HP (HAC-co-AEC), HAC: AEC 2: 1) in embodiment 1;

Fig. 2 is the infrared spectrogram of azide polycarbonate ( ^HP (HAC-co-AEC), HAC: AEC 2: 1) in embodiment 1;

Fig. 3 is the proton nuclear magnetic spectrum of azide polycarbonate ( ^HP (HAC-co-AEC), HAC: AEC 1: 1) in embodiment 2;

Fig. 4 is the ^H -NMR spectrum of the azide polycarbonate (HP(HAC-co-AEC), HAC:AEC 1:2) in Example 3.

Detailed ways

Embodiment 1 synthesizes hyperbranched polycarbonate dPC (HAC: AEC 2: 1) containing azide group

One-pot Synthesis of Hyperbranched Polycarbonate

Synthesis of hyperbranched ^HP (HAC-co-AEC): In a glove box, AC (1g, 5mmol) monomer was dissolved in 10mL of dichloromethane, added to a closed reactor, and then mercaptoethanol ME (197. 27mg, 2.525mmol) and a catalytic amount of triethylamine, reacted at room temperature for 4h. After the reaction time finishes, add the AEC monomer (427.9mg, 2.5mmol) solution that is dissolved in 4mL dichloromethane, then directly add catalyst DBU in the reaction solution, then the reactor is sealed, transfer out glove box, put into 50 The reaction was carried out in an oil bath at ℃ for 48 hours. After the reaction was completed, the reaction was terminated with 2 drops of glacial acetic acid, precipitated in glacial ether, the supernatant was discarded, the transparent oily viscous liquid at the bottom was collected, and the product was obtained by vacuum drying. NMR results show that the ratio of HAC unit and AEC unit in the hyperbranched polymer is 10:1. The infrared spectrum is shown in Figure 2, the absorption peak at 2100cm ^-1 is the characteristic peak of the azide group.

Example 2 Synthesis of hyperbranched polycarbonate dPC (HAC: AEC 1: 1) containing azide group

Synthesis of hyperbranched ^HP (HAC-co-AEC): In a glove box, AC (500mg, 2.5mmol) monomer was dissolved in 8mL of dichloromethane, added to a closed reactor, and then mercaptoethanol ME (394.5 mg, 5.05mmol) and a catalytic amount of triethylamine were reacted at room temperature for 4h. After the reaction time ended, a solution of AEC monomer (427.9 mg, 2.5 mmol) dissolved in 4 mL of dichloromethane was added, and then directly to the reaction solution, catalyst 1,8-diazabicycloundecene-7-ene ( DBU), then seal the reactor well, transfer it out of the glove box, put it into an oil bath at 50°C for 48 hours, stop the reaction with 2 drops of glacial acetic acid after the reaction, precipitate in glacial ether, discard the supernatant, collect The transparent oily viscous liquid at the bottom was vacuum-dried to obtain the product ^HP (HAC-co-AEC). NMR results show that the ratio of HAC unit and AEC unit in the hyperbranched polymer is 5:2.

Embodiment 3 synthesizes the hyperbranched polycarbonate dPC (HAC: AEC 1: 2) of azide group

Synthesis of hyperbranched ^HP (HAC-co-AEC): In a glove box, AC (500mg, 2.5mmol) monomer was dissolved in 8mL of dichloromethane, added to a closed reactor, and then mercaptoethanol ME (394.5 mg, 5.05mmol) and a catalytic amount of triethylamine were reacted at room temperature for 4h. After the reaction time finished, add the AEC monomer (855.8mg, 5mmol) solution that is dissolved in 8mL dichloromethane, then directly add catalyst 1,8-diazabicycloundec-7-ene (DBU ), then seal the reactor well, transfer it out of the glove box, and put it in an oil bath at 50°C for 48 hours. After the reaction, stop the reaction with 2 drops of glacial acetic acid, precipitate in glacial ether, discard the supernatant, and collect the bottom Transparent oily viscous liquid was dried in vacuum to obtain the product ^HP (HAC-co-AEC). NMR results show that the ratio of HAC unit and AEC unit in the hyperbranched polymer is 5:4.

Embodiment 4 synthesis contains the hyperbranched polycarbonate dPC of nitrate group

Synthesis of hyperbranched ^HP (HAC-co-NTC): In the glove box, AC (500mg, 2.5mmol) monomer was dissolved in 8mL dichloromethane, added to the closed reactor, and then mercaptoethanol ME (394.5 mg, 5.05mmol) and a catalytic amount of triethylamine were reacted at room temperature for 4h. After the reaction time ended, a solution of NTC monomer (955 mg, 5 mmol) dissolved in 10 mL of dichloromethane was added, and then the catalyst 1,8-diazabicycloundec-7-ene (DBU) was added directly to the reaction solution , then seal the reactor well, transfer it out of the glove box, and put it in an oil bath at 50°C for 48 hours. After the reaction, terminate the reaction with 2 drops of glacial acetic acid, precipitate in glacial ether, discard the supernatant, and collect the bottom transparent The oily viscous liquid was dried under vacuum to obtain the product ^HP (HAC-co-NTC).

Embodiment 5 synthesis contains the hyperbranched polycarbonate dPC of bromine functional group

Synthesis of hyperbranched ^HP (HAC-co-BTC): In a glove box, AC (500mg, 2.5mmol) monomer was dissolved in 8mL of dichloromethane, added to a closed reactor, and then mercaptoethanol ME (394.5 mg, 5.05mmol) and a catalytic amount of triethylamine were reacted at room temperature for 4h. After the reaction time finished, add the BTC monomer (1.045g, 5mmol) solution that is dissolved in 10mL dichloromethane, then directly add catalyst 1,8-diazabicycloundec-7-ene (DBU ), then seal the reactor well, transfer it out of the glove box, and put it in an oil bath at 50°C for 48 hours. After the reaction, stop the reaction with 2 drops of glacial acetic acid, precipitate in glacial ether, discard the supernatant, and collect the bottom The transparent oily viscous liquid was dried in vacuum to obtain the product ^HP (HAC-co-BTC).

Claims (4)

1. a kind of preparation method of biodegradable functional hyperbranched polycarbonate compound is characterized in that: cyclic carbonate monomer and mercaptoalcohol compound reaction generate and obtain hydroxylated cyclic carbonate, then with Functional hyperbranched polycarbonate compounds obtained by ring-opening polymerization of cyclic carbonates of functional groups; The structural formula of the cyclic carbonate monomer is:

, Wherein R ₁ is selected from H or CH _3; The structural formula of the cyclic carbonate with functional groups is:

, Wherein R ₂ is selected from N ₃ , ONO ₂ , alkynyl or Br functional group. 2. the preparation method of biodegradable functional hyperbranched polycarbonate compound according to claim 1, is characterized in that: described mercapto alcohol compound is selected from the compound of structure as shown below:

, Wherein, R ₃ is selected from C2-C4 alkyl or C4-C8 aryl. 3. The preparation method of the biodegradable functional hyperbranched polycarbonate compound according to claim 1, characterized in that: the ring-opening polymerization catalyst is selected from: 1,8-diazabicycloundec-7 -ene, stannous octoate, 4-dimethylaminopyridine, or zinc bis(bistrimethylsilyl)amine. 4. The application of the biodegradable functional hyperbranched polycarbonate compound prepared by any one of claims 1-3 in the preparation of a drug-controlled release carrier.

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