CN110628008A

CN110628008A - Iodine-containing polycarbonate with X-ray developing function and preparation method and application thereof

Info

Publication number: CN110628008A
Application number: CN201910556064.2A
Authority: CN
Inventors: 俞麟; 马前; 丁建东
Original assignee: Fudan University; Zhuhai Fudan Innovation Research Institute
Current assignee: Fudan University; Zhuhai Fudan Innovation Research Institute
Priority date: 2019-06-25
Filing date: 2019-06-25
Publication date: 2019-12-31
Anticipated expiration: 2039-06-25
Also published as: CN110628008B

Abstract

The invention discloses an iodine-containing polycarbonate with an X-ray developing function, which is prepared by directly introducing iodine atoms onto a polymer skeleton in a chemical bonding manner and has excellent X-ray impermeability or the characteristic of enhancing X-ray absorption. The invention also provides a method for preparing the iodine-containing polycarbonate by the gradual condensation polymerization of the diimidazole ester terminated hydrocarbon compound and the diol compound in the presence of the catalyst, the method has simple and easy material and strong operability, and can obtain developed polycarbonate materials with different compositions and structures and endow the materials with excellent and adjustable X-ray developing performance. Further, the invention also provides application of the iodine-containing polycarbonate in the fields of preparation of developing microspheres and developing particles, visual embolization materials, anti-counterfeiting labels, contrast agents, antibacterial materials, prevention or treatment of iodine deficiency diseases, flame-retardant materials, tissue engineering, drug delivery and the like.

Description

Iodine-containing polycarbonate with X-ray developing function and preparation method and application thereof

Technical Field

The invention belongs to the field of high polymer materials, and particularly relates to an iodine-containing polycarbonate with an X-ray developing function, and a preparation method and application thereof.

Background

CT imaging has been widely used in the fields of clinical diagnosis, material research, tissue engineering, anti-counterfeit technology, etc. because of its advantages of high spatial resolution, deep imaging depth, etc. Various X-ray contrast agents used in combination with these have also been widely developed and used. The addition of metal or inorganic salt particles by physical mixing is the most common and simplest method for preparing X-ray developing materials. However, due to the non-chemical bonding and mixing manner, the added X-ray contrast agent is easy to permeate or leak, so that the developing capability of the material is weakened or lost, and potential systemic toxicity is easily caused when the material is used in the biomedical field. Therefore, how to achieve uniform and strong mixing of the X-ray contrast agent and the matrix material is one of the difficulties faced by those skilled in the art.

In addition, in consideration of the requirements of biocompatibility, controllable degradability and the like of the matrix material, the degradable polycarbonate material becomes one of the most widely applied degradable high polymer materials at present. On this basis, the development of a polycarbonate material containing an X-ray contrast agent is of great importance.

Compared with the traditional physical mixing method, the method has the advantages that the iodine atoms are covalently connected to the polycarbonate skeleton, so that the bonding firmness of the X-ray contrast agent and the matrix material can be ensured, and the uniform functionalization of the polycarbonate material can be realized. At present, there are four main methods for synthesizing functional polycarbonate materials: post-polymerization modification, ring-opening polymerization, addition polymerization, and condensation polymerization. The post-polymerization modification is one of effective methods for synthesizing functional polymers, but has the disadvantages of complicated synthesis steps, incomplete conversion of functional groups, low modification rate and the like. Although ring-opening polymerization is the most common method for synthesizing various polyester or polycarbonate materials, it is now rarely reported for the synthesis of iodine-based polycarbonate functional materials, mainly due to 1) the lack of ubiquitous/commercial iodine-containing monomers; 2) the ring-opening polymerization of polycarbonates is generally only applicable to five-or six-membered ring carbonate monomers derived from 1, 2-ethanediol or 1, 3-propanediol. The ring-opening polymerization method using diiodotrimethylene cyclic carbonate in the prior art has complex synthetic steps and long period, and is not beneficial to industrial popularization or mass production. Another method for polycarbonate synthesis is to employ the addition polymerization of epoxy compounds with carbon dioxide, however, currently, there is no commercially available iodoepoxy compound and chemical synthesis is difficult. In contrast, diol compounds are abundant in nature, while iodoimidazolidine-based compounds containing iodine are relatively easy to prepare, and thus condensation polymerization is a very promising method for iodophor-based polycarbonate materials. However, the conventional condensation polymerization usually requires high temperature and high vacuum reaction conditions, and suffers from problems of continuous removal of small molecules or toxic by-products, thereby limiting the application of the method.

Therefore, the development of an iodine-containing polycarbonate with uniform iodine functional modification, stable developing capability, good degradability and controllable structure and X-ray developing performance and the development of a condensation polymerization method which is simple, easy and strong in operability and can be used for preparing the iodine-containing polycarbonate are the problems to be solved by the technical personnel in the field.

Disclosure of Invention

In view of the above, the present invention provides an iodine-containing polycarbonate having an X-ray developing function, which is directed to the problems of the prior art.

In order to achieve the purpose, the invention adopts the following technical scheme:

an iodine-containing polycarbonate with X-ray developing function, the structural formula of which is any one of a general formula (I) and a general formula (II),

wherein, the block A is a carbonate monomer unit containing iodine, and the block B is a carbonate monomer unit containing no iodine; -ran-for random copolymerization, -alt-for alternating copolymerization; n and m are integers of 2-100.

Preferably, the number average molecular weight of the iodine-containing polycarbonate is 1000-100000.

Preferably, the block A content is from 30 to 70 mol% and the block B content is from 70 to 30 mol%.

It is worth to be noted that the content of the iodine-containing monomer repeating unit in the iodine-containing polycarbonate is closely related to the mass content of iodine atoms in the iodine-containing polycarbonate, and the mass content of the iodine atoms in the iodine-containing polycarbonate is positively related to the developing capability of the iodine-containing polycarbonate. It can be understood that when the iodine atom mass content of the iodine-containing polycarbonate is higher, the developing capability of the iodine-containing polycarbonate is stronger, and the quantitative gray value is higher; when the iodine atom mass content of the iodine-containing polycarbonate is low, the developing capability of the iodine-containing polycarbonate is weak, and the quantitative gray value is lower. Therefore, the present invention specifically defines the content range of the iodine-containing carbonate monomer unit based on the consideration of the stepwise polymerization method and the side reactions thereof, the polymerization reaction conditions, and the selection of the raw materials for stepwise polymerization, but it should be understood that all other contents of the iodine-containing monomer repeating unit obtained by those skilled in the art without creative efforts are within the protection scope of the present invention.

Preferably, the imidazolyl in the general formula (I) or the general formula (II) is replaced by a functional end group, the functional end group is a hydrophilic group or a hydrophobic group, the hydrophilic group is one or more of a hydroxyl group, an amino group, a carboxyl group, an aldehyde group, a cyano group and a nitro group, and the hydrophobic group is one or more of an alkyl group, a sterol group, an alkoxy group, an aromatic heterocyclic group, an amide ester group, a halogen atom, a trichloromethyl group, an ester group, a carbonate group and a mercapto group.

Another object of the present invention is to provide a method for producing the iodine-containing polycarbonate.

In order to achieve the above purpose, the invention provides the following technical scheme:

under the action of a catalyst, a diol compound and a diimidazole compound are gradually polymerized to obtain the iodine-containing polycarbonate, wherein at least one compound in the diol compound and the diimidazole compound comprises at least one iodine atom.

Illustratively, the iodine-containing polycarbonate is obtained by stepwise polymerization of a diol compound containing iodine and a diimidazolyl compound containing no iodine.

Illustratively, the iodine-containing polycarbonate is obtained by stepwise polymerization of a diol compound containing no iodine and a diimidazolyl compound containing iodine.

Illustratively, the iodine-containing polycarbonate is obtained by stepwise polymerizing an iodine-containing diol compound and an iodine-containing diimidazole compound.

Preferably, the catalyst comprises any one of cesium fluoride, cesium chloride, cesium bromide, cesium iodide and tetrabutylammonium fluoride.

Preferably, the structural formula of the diol compound is one or more of the general formulas (III) to (VI),

wherein R is₁～R₁₁Is any one of iodine atom, iodoalkane, hydrogen atom and alkyl; m, n, x, y, k and o are integers of 0-10; and any of the diol compounds contains 0 to 4 iodine atoms.

Preferably, the structural formula of the diimidazole compound is one or more of the general formulas (VII) to (X),

wherein R is₁～R₁₁Is any one of iodine atom, iodoalkane, hydrogen atom and alkyl; m, n, x, y, k and o are integers of 0-10; and any of the above-mentioned diimidazolyl compounds contains 0 to 4 iodine atoms。

Compared with the prior art, the preparation method of the iodine-containing polycarbonate realizes the gradual polymerization of the diol and the diimidazole compound under mild conditions in the presence of a proper catalyst, so that the iodine-containing polycarbonate with a controllable structure is obtained. Due to the wide existence of various diol compounds with different chain lengths or structures in nature, the method provides a rich choice for developing iodine-based polycarbonate with different structural compositions, and is also favorable for conveniently regulating the physicochemical or biological properties of the iodine-based polycarbonate.

It is a further object of the present invention to provide the use of the iodine containing polycarbonates for the preparation of developing materials.

It is worth mentioning that the developing material comprises developing microspheres and developing embedded bodies.

Preferably, the iodine-containing polycarbonate is applied to visual embolism materials, anti-counterfeiting labels, contrast agents, antibacterial materials, iodine deficiency prevention or treatment, flame-retardant materials, tissue engineering and drug delivery systems.

The invention has the advantages that:

on the one hand, the diol starting material employed in this patent is widely and readily available in nature, and the diimidazole compound can also be obtained in high yield by reacting carbonyl diimidazole with the diol starting material. On the other hand, the iodine-containing polycarbonate material provided by the invention directly introduces iodine atoms to a polymer skeleton in a chemical bonding mode, and reduces or overcomes the problems that a small molecule developer and a material are difficult to uniformly mix in the traditional physical blending method and the like. Meanwhile, compared with a small-molecule contrast agent, the iodine-containing polycarbonate material has lower osmotic pressure and fewer side effects. In a word, the iodine-containing polycarbonate material is synthesized by stepwise polymerization, is simple and easy to operate and has strong operability, developing polycarbonate materials with different compositions and structures can be obtained, excellent and adjustable X-ray developing performance is endowed to the materials, and various application requirements can be met.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

Process for preparing 1, 2-diimidazolene ester ethane¹H NMR spectrum.

Process for preparing 1, 3-diimidazole ester propane in figure 2¹H NMR spectrum.

Process for preparing 1, 4-diimidazoleketbutane of FIG. 3¹H NMR spectrum.

Process for preparing 1, 6-diimidazolene ester hexane in figure 4¹H NMR spectrum.

FIG. 5, 1, 8-diimidazole ester base octane¹H NMR spectrum.

Process for preparing 1, 3-diimidazolyl-2, 2-iodomethylpropane in figure 6¹H NMR spectrum.

FIG. 7, of the Polymer PT3-3¹H NMR spectrum.

FIG. 8, polymers PT3-1, PT4-1, PT6-1¹³C NMR spectrum.

FIG. 9 series of polymers PT4¹H NMR spectrum.

FIG. 10, of the Polymer PT6-3¹H NMR spectrum.

FIG. 11 GPC spectra of polymers PT3-1, PT4-1, PT 6-1.

FIG. 12 TGA plots of polymers PT3-1, PT4-1, PT 6-1.

FIG. 13, in vitro Micro-CT 3D reconstructed images of polymers PT3-1, PT4-1, PT6-1, aluminum flake and commercial iodixanol (320mg I/mL).

FIG. 14 is a graph showing the morphology, size distribution and chemical composition of microspheres.

FIG. 15, the whole process of retention of the gastrointestinal tracer visualized microspheres in the digestive tract of ICR mice.

FIG. 16, the visualization characteristics, the in vitro imaging effect of deep tissues and the effect of embedding in bones of the polymer PT4-1 under aluminum sheets with different thicknesses.

FIG. 17, macro-topography and Micro-CT visualization of polymer inlay material by X-ray visualization.

FIG. 18 is a graph showing the effect of long-term tracking of the subcutaneous embedding of polymer-embedded ICR mice.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The present invention will be further specifically illustrated by the following examples for better understanding, but the present invention is not to be construed as being limited thereto, and certain insubstantial modifications and adaptations of the invention by those skilled in the art based on the foregoing disclosure are intended to be included within the scope of the invention.

Example 1

First, 5.24g (84.51mmol) of 1, 2-ethanediol which had been previously dried to remove water was transferred to a bottle in the form of eggplant containing 100mL of anhydrous dichloromethane, 50mL of a dichloromethane solution containing 28.78g (177.48mmol) of carbonyldiimidazole was added dropwise, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the organic solvent is removed from the reaction system through rotary evaporation. Adding 50mL of anhydrous ether-tetrahydrofuran mixed solvent (v/v is 1:1) at-20 ℃ into the reaction bottle, shaking for 10min, performing suction filtration, then rinsing with 5mL of cold tetrahydrofuran for 3 times, drying the filter cake, and storing in a dryer for later use to obtain the 1, 2-diimidazole esterethane, wherein the product is 16.11g, the yield is about 75%, and FIG. 1 shows that the product is the product¹H NMR chart.

Example 2

First, 6.42g (84.37mmol) of 1, 3-propanediol which had been previously dried to remove water was transferred to a bottle in the shape of eggplant containing 100mL of anhydrous methylene chloride, 50mL of a methylene chloride solution containing 28.78g (177.48mmol) of carbonyldiimidazole was added dropwise, and then the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the solvent is removed by rotary evaporation of the reaction system. Adding 50mL of-20 deg.C anhydrous diethyl ether-tetrahydrofuran mixed solvent (v/v ═ 1:1) into the reaction flask, shaking for 10min, vacuum filtering, and concentratingRinsing with 5mL of cold tetrahydrofuran for 3 times, drying the filter cake, and storing in a dryer for use to obtain 20.83g of 1, 3-diimidazole ester propane as white powder with a yield of about 92%, as shown in FIG. 2¹HNMR map.

Example 3

First, 7.61g (84.44mmol) of 1, 4-butanediol dried in advance under vacuum was transferred to a bottle in the shape of a eggplant containing 100mL of tetrahydrofuran, 50mL of a tetrahydrofuran solution containing 28.78g (177.48mmol) of carbonyldiimidazole was added dropwise, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the solvent is removed by rotary evaporation of the reaction system. 50mL of an anhydrous ethyl acetate-anhydrous ether mixed solvent (v/v ═ 1: 3) at-20 ℃ is added into the reaction flask, the mixture is shaken for 10min, then is filtered by suction, and is rinsed 3 times with 5mL of cold tetrahydrofuran, and the filter cake is dried in vacuum at 25 ℃ overnight to obtain 21.43g of 1, 4-diimidazole esterbutane as a white powder with a yield of 90%, wherein FIG. 3 shows that the white powder is¹H NMR chart.

Example 4

9.98g (84.45mmol) of 1, 6-hexanediol which had been dried in advance was put into a jar containing 100mL of anhydrous ethyl acetate, 50mL of an ethyl acetate solution containing 28.78g (177.48mmol) of carbonyldiimidazole was added dropwise, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the solvent is removed by rotary evaporation of the reaction system. 50mL of an anhydrous ethyl acetate-tetrahydrofuran mixed solvent (v/v ═ 1: 4) at-20 ℃ was added to the above reaction flask, shaken for 10min, filtered, the filter cake was washed 3 times with 5mL of tetrahydrofuran, and the filter cake was dried under vacuum at room temperature overnight to give 23.56g of 1.6-diimidazole esterhexane as a white powder, with a yield of 90%, which is shown in FIG. 4¹H NMR chart.

Example 5

First, 12.35g (84.46mmol) of 1, 8-octanediol dried in advance was put into a jar containing 100mL of anhydrous ethyl acetate, 50mL of an ethyl acetate solution containing 28.78g (177.48mmol) of carbonyldiimidazole was added dropwise, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the solvent is removed by rotary evaporation of the reaction system. 50mL of an anhydrous ethyl acetate-tetrahydrofuran mixed solvent (v/v ═ 1: 4) at-20 ℃ is added into the reaction bottle, the mixture is shaken for 10min and then filtered, the filter cake is washed with 5mL of tetrahydrofuran for 3 times, the filter cake is dried in vacuum at room temperature overnight, 27.14g of 1, 8-diimidazole ester octane is obtained,yield 95%, FIG. 5 is it¹H NMR chart.

Example 6

First, 11.67g (84.60mmol) of o-xylene glycol which had been dried in advance was put in a jar containing 100mL of anhydrous ethyl acetate, 50mL of an ethyl acetate solution containing 28.78g (177.6mmol) of carbonyldiimidazole was added dropwise, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the solvent is removed by rotary evaporation of the reaction system. 50mL of an anhydrous ethyl acetate-tetrahydrofuran mixed solvent (v/v ═ 1: 4) at-20 ℃ is added into the reaction bottle, the mixture is shaken for 10min and then filtered, the filter cake is washed with 5mL of tetrahydrofuran for 3 times, and the filter cake is dried in vacuum at room temperature overnight, so that 26.50g of o-dimethyldiimidazole ester benzene is obtained, and the yield is 95%.

Example 7

Firstly, 15.05g (42.29mmol) of 2, 2-diiodomethyl-1, 3-propanediol which is dehydrated is added into a round-bottom flask containing 50mL of ethyl acetate, 28.78g (177.48mmol) of carbonyldiimidazole is added into 50mL of ethyl acetate solution, the mixture reacts for 24h at room temperature, then the solvent is removed by rotary evaporation, and the product is dried by spinning. 80mL of an anhydrous ethyl acetate-tetrahydrofuran mixed solvent (v/v ═ 1: 4) at-20 ℃ was added to the above reaction flask, shaken for 10min, filtered, the filter cake was washed with 3 times with 10mL of tetrahydrofuran, and finally dried overnight under vacuum to give 21.08g of 1, 3-diimidazolyl-2, 2-diiodomethylpropane in 91% yield, which is shown in FIG. 6¹H NMR chart.

Example 8

Firstly, 21.3g (80.67mmol) of 4-iodophthalic alcohol with water removed is added into a round-bottom flask containing 100mL of ethyl acetate, 50mL of a carbonyl diimidazole 28.78g (177.48mmol) ethyl acetate solution is added, the mixture is reacted for 24 hours at room temperature, and then the solvent is removed by rotary evaporation and is dried in a rotary manner. 80mL of an anhydrous ethyl acetate-tetrahydrofuran mixed solvent (v/v ═ 1: 2) at-20 ℃ is added into the reaction bottle, the mixture is shaken for 10min and then filtered, then the filter cake is washed with 10mL of anhydrous tetrahydrofuran for 3 times, and finally the filter cake is dried in vacuum overnight to obtain 33.5g of 1, 2-diimidazolylmethylene-4-iodobenzene with the yield of 92%.

Example 9

2.22g (8.88mmol) of dried small molecule compound 1, 2-diimidazolene ester ethane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction flaskAdding 12.8mg (0.084mmol) of cesium fluoride under anhydrous and oxygen-free conditions, uniformly mixing, then adding 10mL of anhydrous dichloromethane, and heating the system to 35 ℃ under an argon atmosphere to react for 17 hours. After natural cooling, the polymer solution was precipitated by pouring into 100mL of cold methanol with high-speed stirring. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 1.31g of PT1 polymer in 25% yield. The molecular weight distribution coefficient (M) was determined by Gel Permeation Chromatography (GPC) using N, N-Dimethylformamide (DMF) as the mobile phase_w/M_n) Has a number average molecular weight (M) of 1.73_n) Is 3500.

Example 10

2.34g (8.88mmol) of dried 1, 3-diimidazolene ester propane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction flask, 64mg (0.42mmol) of cesium fluoride (cesium fluoride) is added and mixed uniformly, the mixture is melted and reacted for 3h at 100 ℃, and after natural cooling, the mixture is poured into 100mL of cold methanol stirred at high speed for precipitation. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 2.41g of PT2 polymer. Determination of the molecular weight distribution coefficient (M) by Gel Permeation Chromatography (GPC) using DMF as the mobile phase_w/M_n) Has a number average molecular weight (M) of 1.78_n) It was 5000.

Example 11

2.34g (8.88mmol) of dried 1, 3-diimidazole ester propane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction bottle, 12.8mg (0.084mmol) of cesium fluoride is added under the anhydrous and oxygen-free conditions and mixed uniformly, 10mL of anhydrous tetrahydrofuran is added, the system is heated to 60 ℃ under argon atmosphere for reaction for 17h, and finally 5mL of end-capping reagent anhydrous methanol is added for further reaction for 15 h. After natural cooling, the polymer solution was precipitated by pouring into 100mL of cold methanol with high-speed stirring. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to yield 2.41g of the polymer product methyl terminated PT 3-1. Meanwhile, the preparation method of the phenyl-terminated PT3-2 polymer is similar to that of the polymer, except that 5mL of the end-capping reagent of anhydrous methanol is changed into 1.5mL of anhydrous benzyl alcohol for reaction, and other conditions are the same; the imidazole-terminated PT3-3 polymer is reacted without adding any capping agentDirectly precipitating for 17 h. The glass transition temperature T of PT3-1 is obtained by a differential scanning calorimeter test_gThe thermal decomposition initiation temperature T of PT3-1 was determined by TGA testing at 16 ℃_d230 ℃ (temperature at which 5% weight loss occurs). The molecular weight distribution coefficient (M) of PT3-1 was determined by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.61_n) Is 2800. FIG. 7 shows PT3-3¹H NMR chart (imidazolyl terminated polymer), FIG. 8 is of PT3-1¹³C NMR, FIG. 12 is a thermogravimetric analysis of PT3-1, taken in combination¹H NMR and¹³c NMR showed that the PT3 series polymer was a polymer of an alternating structure, and the molar composition of the iodine-containing monomer units in the polymer sequence was 50%.

Example 12

2.47g (8.88mmol) of dried 1, 4-diimidazole ester butane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are added into a 50mL reaction bottle, 63.8mg (0.42mmol) of cesium fluoride is added under anhydrous and oxygen-free conditions and mixed uniformly, 10mL of anhydrous tetrahydrofuran is added, the system is heated to 60 ℃ under argon atmosphere for reaction for 17h, and finally 5mL of end-capping reagent anhydrous methanol is added for further reaction for 15 h. After natural cooling, the crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation. After the supernatant liquid is poured off, 5mL of cold methanol is added into the precipitate every time for washing for 3 times, and 2.73g of PT4-1 polymer product is obtained after drying. Wherein, the preparation method of the phenyl-terminated PT4-2 polymer is similar to that of the polymer, 5mL of the end-capping reagent anhydrous methanol is changed into 1.5mL of anhydrous benzyl alcohol for reaction, and other conditions are the same; the imidazole-terminated PT4-3 polymer is directly precipitated after reacting for 17 hours without adding any capping agent. The molecular weight distribution coefficient (M) of PT4-1 was determined by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.45_n) Is 2500. The glass transition temperature T of PT4-1 is obtained by a differential scanning calorimeter test_gThe thermal decomposition initiation temperature T of PT4-1 was determined by TGA test at-12 ℃_d190 ℃. FIG. 8 shows PT4-1¹³C NMR chart, FIG. 9 is of three different terminal polymers¹H NMR chart, FIG. 11 is gel permeation chromatogram of PT4-1, and FIG. 12 is thermogravimetric analysis of PT4-1Figure (a). Bonding of¹H NMR and¹³c NMR showed that the PT-4 series polymer was a random polymer having a molar composition of 48% of iodine-containing monomer units in the polymer sequence.

Example 13

2.97g (8.88mmol) of dried 1, 8-diimidazole ester octane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction bottle, 64mg (0.42mmol) of cesium fluoride is added under anhydrous and oxygen-free conditions and mixed uniformly, 10mL of tetrahydrofuran is added, the mixture is heated to 60 ℃ under argon atmosphere and reacted for 17 hours, and the mixture is cooled naturally. The crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation, supernatant liquid is poured out, 5mL of cold methanol is added for washing for 3 times, and the product of PT5 polymer 1.79g is obtained after drying. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.82_n) And 6800.

Example 14

2.72g (8.88mmol) of dried 1, 6-diimidazole esterhexane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction bottle, 63.8mg (0.42mmol) of cesium fluoride is added under anhydrous and oxygen-free conditions and mixed uniformly, 10mL of anhydrous ethyl acetate is added, the mixture is heated to 60 ℃ under argon atmosphere for reaction for 17h, and finally 5mL of end-capping reagent anhydrous methanol is added for reaction for further 15 h. After natural cooling, the crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation, the supernatant liquid is poured out, 5mL of cold methanol is added for washing for 3 times, and 2.55g of PT6-1 polymer product is obtained after drying. Wherein, the preparation method of the phenyl-terminated PT6-2 polymer is similar to that of the polymer, 5mL of the end-capping reagent anhydrous methanol is changed into 1.5mL of anhydrous benzyl alcohol for reaction, and other conditions are the same; the imidazole-terminated PT6-3 polymer is directly precipitated after reacting for 17 hours without adding any capping agent. Molecular weight distribution coefficient (M) of PT6-1 determined by gel permeation chromatography_w/M_n) Has a number average molecular weight (M) of 1.64_n) Is 4000. The glass transition temperature T of PT6-1 is obtained by a differential scanning calorimeter test_gThe thermal decomposition initiation temperature T of PT6-1 was determined by TGA test at-10 ℃_dAt 210 deg.c. FIG. 8 shows PT6-1¹³CNMR map, FIG. 10 is of PT6-3¹H NMR chart (imidazole terminated polymer), FIG. 11 is gel permeation chromatogram of PT6-1, and FIG. 12 is thermogravimetric analysis chart of PT 6-1. Bonding of¹H NMR and¹³the PT6 series polymer is a random polymer, and the molar composition of the iodine-containing monomer units in the polymer sequence is 47 percent according to C NMR.

Example 15

4.01g (8.88mmol) of dried 1, 2-diimidazolethylene-4-iodobenzene and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction bottle, 26mg (0.168mmol) of cesium fluoride is added and mixed uniformly, vacuum-argon is circulated for three times, and then the system is heated to 100 ℃ for melting reaction for 3 hours. After natural cooling, 2mL of DMF was added to dissolve the crude product, which was then poured into 100mL of cold methanol with high stirring to precipitate. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 4g of PT7 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.78_n) Is 96000.

Example 16

2.72g (8.88mmol) of dried 1, 6-diimidazolene ester hexane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol are put into a 50mL reaction flask, 85mg (0.504mmol) of CsCl is added and mixed uniformly, vacuum-argon is circulated for three times, then the mixture is heated to 100 ℃ for melting reaction for 3h, and the mixture is naturally cooled. The crude product was directly poured into 100mL of cold methanol with high speed stirring for precipitation, the supernatant was decanted and 5mL of cold methanol was added for washing 3 times to obtain 3.52g of PT8 polymer product after drying. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.48_n) Is 4500.

Example 17

2.97g (8.88mmol) of dried 1, 8-diimidazolene ester octane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol were put into a 50mL reaction flask, 85mg (0.504mmol) of CsBr was added thereto and mixed well, 10mL of tetrahydrofuran solution was added thereto and heated to 60 ℃ to react for 17 hours. After natural cooling, the crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation, the supernatant is poured off and 5mL of the supernatant is addedThe product was washed 3 times with cold methanol and dried to give 3.52g of PT9 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.68_n) Is 6300.

Example 18

2.47g (8.88mmol) of dried 1, 4-diimidazolene butane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol were put into a 50mL reaction flask, 132mg (0.504mmol) of tetrabutylammonium fluoride was added thereto and mixed well, 10mL of tetrahydrofuran solution was added thereto, followed by reaction at 60 ℃ for 17 hours and natural cooling. The crude product was directly poured into 100mL of cold methanol with high speed stirring for precipitation, the supernatant was decanted and 5mL of cold methanol was added for washing 3 times to obtain 3.52g of PT10 polymer product after drying. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.59_n) Is 3800.

Example 19

Putting 2.72g (8.88mmol) of dried 1, 6-diimidazole esterhexane and 3.01g (8.46mmol) of 2, 2-diiodomethyl-1, 3-propanediol into a 50mL reaction bottle, adding 13mg (0.084mmol) of cesium fluoride, uniformly mixing, heating to 100 ℃ after three times of vacuum-argon circulation for melting reaction for 5 hours, continuously vacuumizing to remove sublimed imidazole micromolecules, and naturally cooling. The crude product was directly poured into 100mL of cold methanol with high speed stirring for precipitation, the supernatant was decanted and 5mL of cold methanol was added for washing 3 times, and the product was dried to give 3.5g of PT11 polymer. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.55_n) 26800.

Example 20

0.675g (8.88mmol) of dried 1, 3-propanediol and 4.6g (8.46mmol) of 1, 3-diimidazolyl-2, 2-iodomethylpropane are put into a 50mL reaction bottle, 78mg (0.504mmol) of cesium fluoride is added and mixed uniformly, vacuum-argon is circulated three times, and then the system is heated to 100 ℃ for melting reaction for 3 hours. After natural cooling, 2mL of DMF was added to dissolve the crude product, which was then poured into 100mL of cold methanol with high stirring to precipitate. After decanting the supernatant, 5mL portions of cold methanol were added to the pelletAfter washing for 3 times and drying, 2.65g of PT12 polymer product is obtained. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.80_n) Is 3000.

Example 21

0.8g (8.88mmol) of dried 1, 4-butanediol and 3.65g (8.46mmol) of 1, 5-diimidazolyl-2-iodomethylpentane are taken and added to a 50mL reaction flask, 78mg (0.504mmol) of cesium fluoride is added and mixed uniformly, vacuum-argon is circulated three times, and then the system is heated to 100 ℃ for melting reaction for 3 hours. After natural cooling, the crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to obtain 2.78g of PT13 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.57_n) Is 4700.

Example 22

1.05g (8.88mmol) of dried 1, 6-hexanediol and 4.6g (8.46mmol) of 1, 3-diimidazolyl-2, 2-iodomethylpropane were put into a 50mL reaction flask, 78mg (0.504mmol) of cesium fluoride was added thereto and mixed well, and the mixture was heated to 100 ℃ for melting reaction for 3 hours after three cycles of vacuum-argon. After natural cooling, the crude product is directly poured into 100mL of cold methanol with high-speed stirring for precipitation, the supernatant liquid is poured out, 5mL of cold methanol is added for washing for 3 times, and 3.65g of PT14 polymer product is obtained after drying. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.62_n) Was 4800.

Example 23

2.34g (8.88mmol) of dried 5-iodo-m-benzenedimethanol and 4.6g (8.46mmol) of 1, 3-diimidazole ester group-2, 2-iodo-methylpropane are put into a 50mL reaction flask, 78mg (0.504mmol) of cesium fluoride is added and mixed uniformly, vacuum-argon is circulated for three times, the system is heated to 100 ℃ for melting reaction for 3 hours, and imidazole is removed continuously by vacuumizing. After natural cooling, 2mL of DMF was added to dissolve the crude product, which was then poured into 100mL of cold methanol with high stirring to precipitate. After decanting the supernatant, 5mL portions of cold methanol were added to the pelletAfter 3 times of washing and drying, PT15 polymer product is obtained with 68% yield. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.86_n) Is 18000.

Example 24

1.05g (8.88mmol) of dried 1, 6-hexanediol and 3.54g (8.46mmol) of 1, 4-diimidazolyl-2-iodomethylbutane were put into a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed uniformly, vacuum-argon was circulated three times, and the mixture was heated to 100 ℃ to melt and react for 5 hours, and imidazole was removed by continuous vacuum evacuation. After natural cooling, the crude product was directly poured into 100mL of cold methanol with high speed stirring for precipitation, the supernatant was poured off and 5mL of cold methanol was added for washing 3 times, and after drying, 3.62g of PT16 polymer product was obtained with a yield of 65%. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.48_n) Is 26000.

Example 25

0.8g (8.88mmol) of dried 1, 4-butanediol and 4.6g (8.46mmol) of 1, 3-diimidazolyl-2, 2-iodomethylpropane were taken and charged in a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed well, 4.5mL of DMFj was added, and the system was heated to 60 ℃ to react for 20 hours. Most of DMF in the system was removed by distillation under reduced pressure, and the crude product was directly poured into 100mL of cold methanol with high-speed stirring for precipitation. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 3.5g of PT17 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.45_n) Was 13000.

Example 26

1.05g (8.88mmol) of dried 1, 6-hexanediol and 4.6g (8.46mmol) of 1, 3-diimidazolyl-2, 2-iodomethylpropane were taken and put into a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed uniformly, vacuum-argon was circulated three times, 4.5mL of ethyl acetate was added, and the system was heated to 60 ℃ to react for 24 hours. Most of the ethyl acetate in the system was removed by rotary evaporation, and the crude product was poured directly into 100mL of cold methanol with high stirring speedAfter precipitation, the supernatant was decanted and washed 3 times with 5mL of cold methanol, and dried, 3.68g of PT18 polymer product was obtained. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.65_n) 21800.

Example 27

2.34g (8.88mmol) of dried 5-iodoisophthal and 4.01g (8.46mmol) of 1, 8-diimidazolyl-4-iodomethyloctane were put in a 50mL reaction flask, 39mg (0.252mmol) of cesium fluoride was added thereto and mixed uniformly, 4.5mL of DMFj was added thereto, and the system was heated to 60 ℃ to react for 26 hours. Most of the DMF was distilled off under reduced pressure and then precipitated by pouring into 100mL of cold methanol with high stirring. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 2.73g of PT19 polymer product. Determination of the molecular weight distribution coefficient (M) by Gel Permeation Chromatography (GPC) using DMF as the mobile phase_w/M_n) Has a number average molecular weight (M) of 1.75_n) Was 13000.

Example 28

0.8g (8.88mmol) of dried 1, 4-butanediol and 3.65g (8.46mmol) of 1, 5-diimidazolyl-3-iodomethylpentane were taken and charged into a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed uniformly, 4.5mL of DMFj was added, the system was heated to 60 ℃ for reaction for 20 hours, and then 3g of excess p-hydroxybenzaldehyde was added and the reaction was continued for 48 hours. Most of DMF in the system was removed by distillation under reduced pressure, and the crude product was directly poured into 100mL of cold methanol with high-speed stirring for precipitation. After the supernatant liquid is poured off, 5mL of cold methanol is added into the precipitate every time for washing for 3 times, and after drying, 3.2g of aldehyde-terminated PT20 polymer product is obtained. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.65_n) 7000.

Example 29

1.05g (8.88mmol) of dried 1, 6-hexanediol and 3.77g (8.46mmol) of 1, 6-diimidazolyl-3-iodomethylhexane were put in a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed well, 4.5mL of ethyl acetate was added after three cycles of vacuum-argon, the system was heated to 60 ℃ for reaction for 24 hours, and excess n-butanol 2 was added.8 g. Most of the ethyl acetate in the system was removed by rotary evaporation, and then the crude product was directly poured into 100mL of cold methanol with high speed stirring for precipitation, the supernatant was decanted and washed 3 times with 5mL of cold methanol, and dried to give 3.28g of alkyl terminated PT21 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.75_n) Is 5800.

Example 30

0.675g (8.88mmol) of dried 1, 3-propanediol and 3.54g (8.46mmol) of 1, 4-diimidazolyl-2-iodomethylbutane were taken and put into a 50mL reaction flask, 65mg (0.42mmol) of cesium fluoride was added and mixed uniformly, 4.5mL of ethyl acetate was added after three cycles of vacuum-argon, the system was heated to 60 ℃ for reaction for 24h, and excess 3-bromo-1-propanol was added and the reaction was continued for 30 h. After natural cooling, 2mL of DMMF was added to dissolve the crude product, which was then precipitated by pouring into 100mL of cold methanol with high stirring. After the supernatant was decanted, the precipitate was washed 3 times with 5mL portions of cold methanol and dried to give 2.55g of the bromine-containing PT22 polymer product. Determination of the molecular weight distribution coefficient (M) by gel permeation chromatography (using DMF as mobile phase)_w/M_n) Has a number average molecular weight (M) of 1.60_n) Is 4500.

To further verify the excellent effects of the present invention, the inventors also conducted the following experiments:

experimental example 1

PT3-1, PT4-1, PT6-1, aluminum sheets and iodixanol (320mg I/mL) are respectively placed in a PMMA organic glass tube and sealed, and scanning shooting is carried out by using a Micro-CT under the same condition. The development effects of PT3-1, PT4-1, PT6-1, aluminum flake and iodixanol are shown in FIG. 13A, where the values are the quantitative average gray values. Subsequent animal subcutaneous embedding imaging experiments (as shown in fig. 13B) also demonstrated that PT4-1 iodopolycarbonate material can be clearly distinguished from soft tissue and can be used as a contrast agent.

Experimental example 2

1.08g of the polymer PT4-1 and 3.2g of polylactic acid PLA (viscosity: 7.0X 10)^-6m²/s) was added to 11.3g of methylene chloride and dissolved overnight, after shaking it uniformly, it was poured into 50mL of a 0.4 wt% aqueous solution of PVAThe solution was stirred with a high speed homogenizer at 6000rpm for two minutes. The emulsion was poured into 1280mL of water, stirred at room temperature for 30 minutes, and then warmed to 40 ℃ to cure for 6 hours. Filtration, washing with water (5X 40mL), and vacuum drying afforded 1.4g of polymeric microspheres in 55% yield. The morphology of the polymer microspheres is characterized by Micro-CT (fig. 14A) and FESEM (fig. 14B), and the morphology is a regular spherical structure. The particle size and particle size distribution were measured by a laser particle size analyzer (FIG. 14C), and the average particle size was 135. mu.m. The nuclear magnetization showed that the PVA had been completely removed (fig. 14D). It can be seen that PT4-1 can be used as a macromolecular contrast agent for preparing X-ray microspheres with uniform size.

Experimental example 3

30mg of 135-micron polymer PT4/PLA microspheres are uniformly dispersed in 0.15mL of 0.2 wt% Tween 80 aqueous solution, then the microsphere solution is injected into the stomach of a mouse by using a stomach filling needle, and Micro-CT scanning is carried out at 0.5h, 5h and 10h after stomach filling respectively, and the result is shown in figure 15. The retention process of the microspheres in the gastrointestinal tract over time can be traced by Micro-CT imaging. The PT4-1 macromolecular contrast agent microspheres can be used for tracking digestive tract imaging under CT imaging, can resist physiological conditions such as gastric acid and have basic properties for digestive tract contrast agents.

Experimental example 4

The result of taking a plurality of PT4-1 polymer sheets with the thickness of 0.5mm, aluminum sheets with different thicknesses and pork tissues and carrying out X-ray scanning by X-treme under the same condition shows that the polymer sheets with the thickness of 0.5mm have development strength equivalent to that of the aluminum sheets with the thickness of 3mm, and the morphological characteristics of the polymer sheets can be clearly seen by X-rays even if the polymer sheets are shielded by the aluminum sheets with the thickness of 5mm or the pork with the thickness of 70mm, which shows that the polymer PT4-1 has the characteristic of deep tissue development, and the subsequent in-vitro animal bone embedding imaging experiment also proves the advantage, and is particularly shown in figure 16. The PT4-1 polymer can be seen to be distinguished from surrounding soft tissues and bones, the boundary is clear, the X-ray imaging intensity is also obviously superior to that of bones, and the PT4-1 polymer has the capability of being applied to deep tissue contrast agents

Experimental example 5

0.5g of polymer PT4-1 and 1.5g of polylactic acid PLA (viscosity: 7.0X 10-6m2/s) were added to 2.5g of dichloromethane and dissolved overnight, and after being mixed uniformly, the mixture was naturally evaporated and dried. And (3) placing the dried samples into polymer embedding body molds with different shapes and sizes, softening and compacting at 55 ℃, taking out, and naturally cooling and forming. The morphology of the polymer embedded bodies was photographed and characterized by a camera and Micro-CT, respectively, and as shown in fig. 17 in particular, the addition of the contrast agent PT4-1 can impart superior X-ray visualization effect to the polymer embedded bodies. As shown in fig. 18, further long-term tracking experiments under ICR mouse skin showed that the polymer implant could be imaged in a period of up to 2 months and could reflect the morphological changes of the polymer implant, and has the basic properties of being applied to in vivo visualization materials.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An iodine-containing polycarbonate with X-ray developing function is characterized in that the structural formula is any one of a general formula (I) and a general formula (II),

2. The iodine-containing polycarbonate with X-ray developing function as defined in claim 1, wherein the number average molecular weight of the iodine-containing polycarbonate is 1000-100000.

3. The iodine-containing polycarbonate having an X-ray developing function according to claim 1, wherein the content of the block A is 30 to 70 mol% and the content of the block B is 70 to 30 mol%.

4. The iodine-containing polycarbonate with the X-ray developing function according to claim 1, wherein the imidazolyl group in the general formula (I) or the general formula (II) is replaced by a functional end group, the functional end group is a hydrophilic group or a hydrophobic group, the hydrophilic group is one or more of a hydroxyl group, an amino group, a carboxyl group, an aldehyde group, a cyano group and a nitro group, and the hydrophobic group is one or more of an alkyl group, a sterol group, an alkoxy group, an aromatic heterocyclic group, an amide ester group, a halogen atom, a trichloromethyl group, an ester group, a carbonate group and a mercapto group.

5. The method for preparing iodine-containing polycarbonate according to any one of claims 1 to 3, wherein the iodine-containing polycarbonate is obtained by stepwise polymerizing a diol compound and a diimidazolyl compound, wherein at least one of the diol compound and the diimidazolyl compound comprises at least one iodine atom, in the presence of a catalyst.

6. The method of claim 5, wherein the catalyst comprises any one of cesium fluoride, cesium chloride, cesium bromide, cesium iodide, tetrabutylammonium fluoride.

7. The method of claim 5, wherein the diol compound has one or more of the formulae (III) to (VI),

wherein R is₁～R₁₁Relatively independently is any one of iodine atom, iodoalkane, hydrogen atom and alkyl; m, n, x, y, k and o are integers of 0-10; and any of the diol compounds contains 0 to 4 iodine atoms.

8. The method according to claim 5, wherein the diimidazole compound has one or more of the general formulas (VII) to (X),

wherein R is₁～R₁₁Relatively independently is any one of iodine atom, iodoalkane, hydrogen atom and alkyl; m, n, x, y, k and o are integers of 0-10; wherein any of the diimidazole compounds contains 0 to 4 iodine atoms.

9. Use of the iodine containing polycarbonate of any of claims 1 to 4 in the preparation of a developer material.

10. The use of an iodine containing polycarbonate of claim 9, wherein said iodine containing polycarbonate is used in a visual embolization material, a security label, a contrast agent, an antimicrobial material, a prophylaxis or treatment of iodine deficiency diseases, a fire retardant material, tissue engineering, a drug delivery system.