CN103897181A - Polymer, and preparation method and application thereof - Google Patents
Polymer, and preparation method and application thereof Download PDFInfo
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- CN103897181A CN103897181A CN201210578771.XA CN201210578771A CN103897181A CN 103897181 A CN103897181 A CN 103897181A CN 201210578771 A CN201210578771 A CN 201210578771A CN 103897181 A CN103897181 A CN 103897181A
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Abstract
The invention is applicable to the field of high polymer materials and provides a polymer and a preparation method and application thereof. The polymer has a structural formula as described in the specification. The polymer comprises a polyoxazoline group and one selected from the group consisting of an ester group, a carboxyl group, an amino group, a hydroxyl group, a mercapto group, an azido group and a trimethoxy(triethoxy)silicyl group. With the polyoxazoline group, the polymer has excellent biological inertness, stability and easy synthesis performance; with active functional groups consisting of the amino group, the carboxyl group, the hydroxyl group, the mercapto group, the azido group, the trimethoxy(triethoxy)silicyl group and the like, the polymer can undergo a cross-linking reaction with functional groups having other properties, so the application scope of the polymer is substantially widened. According to the preparation method for the polymer, the polyoxazoline group and other active functional groups are introduced so as to realize excellent biological inertness, stability and easy synthesis performance of the polymer and to allow the polymer to be capable of undergoing a cross-linking reaction with functional groups having other properties and to have a wider application scope.
Description
Technical field
The invention belongs to polymeric material field, relate in particular to a kind of polymkeric substance, its preparation method and application.
Background technology
In recent decades, because biomedical product is as artificial implant, medicament carrier system, the rapid growth of the demands such as image-forming contrast medium and biochip, the application fast development of antifouling (also claiming biologically inert) macromolecular material aspect surface-coating.In addition, these materials are as antibacterial in food product pack in antimicrobial growth field, refrigerator lining is antibacterial, the anti-algal grown of antibacterial fabric and boats and ships surface etc. also has huge application prospect.Generally speaking, these macromolecular materials have the features such as hydrophilic, electric neutrality, hydrogen bond receptor.When these materials are modified after solid surface, can high degree of hydration in the aqueous solution.In the situation that percentage of grafting, molecular weight etc. are optimized, by volume steric effect, entropy effect and infiltration repelling effect, can stop the spontaneous absorption of protein and subsequently as bioprocesss such as bacteria breeds.
It has been generally acknowledged that, the artificial embedded material that lacks biologically inert enters after human body, and the protein of its surface adsorption can produce important effect to many bioprocesss, such as thrombosis, external source body rejection and bacterium infection etc.Aspect medicament carrier system and image-forming contrast medium; nano particle or Nano capsule that research surface has the protection of anti-soil macromolecular material possess more macrocyclic blood circulation; thereby before making it by the netted endomembrane system of human body or nephridial tissue removing, can in human recycle system, stop the longer time.Aspect biochip, anti-soil macromolecular material is generally used for building biologically inert background surface, makes specific protein adsorption only occur in the region needing.
In these macromolecular materials, polyoxyethylene glycol is that application is maximum.The success of polyoxyethylene glycol is its wetting ability, also has high biocompatibility with the low affinity of blood ingredient.
Although its performance is outstanding aspect anti-protein adsorption, it also has larger defect result of study surface in recent years.For example, research finds that the mechanism of action it be unclear that by certain through polyethyleneglycol modified lipid physical efficiency causes complement activation, thereby causes allergic reaction or even anaphylactic shock.In addition find that the polyethyleneglycol modified liposome of biphasic injection can cause the acceleration blood clean phenomenon that may be caused by immune response.There are some researches show that, in long-term live body test, the meeting oxidative degradation of polyoxyethylene glycol coating also loses its biological function simultaneously.The mechanism of degradation of polyoxyethylene glycol is very complicated.Some cell, as scavenger cell and multinuclear leucocyte, can secrete can oxidative degradation polyoxyethylene glycol the active oxidation factor, as super-oxide, hydrogen peroxide, nitrogen protoxide.In the preparation process of polyoxyethylene glycol or polyethyleneglycol derivative, polyoxyethylene glycol at high temperature also can be by thermooxidative degradation in air.In addition, report, polyoxyethylene glycol high temperature under oxygen free condition also can be degraded.
Summary of the invention
The object of the present invention is to provide a kind of polymkeric substance, to substitute polyoxyethylene glycol, solve the bad problem of polyethylene glycol stabilized property.
The present invention is achieved in that
A kind of polymkeric substance, has following chemical structural formula:
Wherein, the random natural number that n is 20-120, R
1for hydrogen atom, methyl or ethyl, R
2for end is with the group of amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (or second) TMOS base.
And,
Above-mentioned method for producing polymer, comprises the steps:
2-methyl-2-oxazoline and initiator are added in organic solvent, are to react 6-48 hour under 60-80 ℃ of condition in temperature;
Temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, by the stirring of removing, add water of solvent in solution after reaction, be 9-14 Water Under solution 2-36 hour by the reaction product adding water after stirring in pH value, pH after hydrolysis is adjusted to 6-8, dialysis obtains polymkeric substance, this initiator is selected from 3-ethyl bromide or 3-methyl bromide c, and this terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-or front three (second) TMOS base;
Or,
Temperature is adjusted to room temperature, adds terminator, stirring reaction 2-24 hour, removes solution solvent part after reaction to obtain thick solution, then solution is added in ether, obtains white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtain polymkeric substance.Described terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-or front three (second) TMOS base.
Or,
Temperature is adjusted to room temperature, decompression heating is by the reaction solution solvent stirring of removing, add water afterwards again, the reaction product adding water after stirring is hydrolyzed to 2-36 hour in pH value for (using sodium hydroxide or potassium hydroxide as alkali) under 9-14 condition, pH after hydrolysis is adjusted to 6-8, the dry polymkeric substance that obtains of dialysis.
Polymkeric substance of the present invention, comprises poly-oxazoline group and ester group or carboxyl and amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base group.By this poly-oxazoline group, polymkeric substance of the present invention has very excellent biologically inert, stability and easily synthetic, by this amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base isoreactivity functional group, make this polymkeric substance crosslinking reaction to occur with the functional group of other character, greatly widened the range of application of this polymkeric substance; Method for producing polymer of the present invention, by introducing poly-oxazoline group and other active function groups, realize this bright polymkeric substance and there is very excellent biologically inert, stability and easily synthetic, and can crosslinking reaction occur with the functional group of other character, there is wide range of application.
Accompanying drawing explanation
Fig. 1 is the 1H-nuclear magnetic spectrogram of the polymkeric substance prepared of the embodiment of the present invention one.
Embodiment
In order to make object of the present invention, technical scheme and advantage clearer, below in conjunction with drawings and Examples, the present invention is further elaborated.Should be appreciated that specific embodiment described herein, only in order to explain the present invention, is not intended to limit the present invention.
Poly-(2-methyl-2-oxazoline) can be regarded as on the nitrogen-atoms of each repeating unit of polymine and connected an acetyl group.On the one hand, this material has the vinyl-heteroatoms similar to polyoxyethylene glycol and replaces repeated arrangement structure.In addition on the one hand, owing to having the structure of polypeptide isomer, this material also belongs to class fret peptide family simultaneously.Because have amide group in structure, poly-(2-methyl-2-oxazoline) is an extraordinary hydrogen bond receptor.As hydrophilic material, it has shown good anti-protein adsorption characteristic.Poly-(2-methyl-2-oxazoline) occurs as the liposome of coating, and in blood, has longer cycling time.Channel protein is embedded to the softgel shell being assembled into by three sections of multipolymers (poly-(2-methyl-2-oxazoline)-polydimethyl silane-poly-(2-methyl-2-oxazoline)) and also developed the nano-reactor of preparing.Research shows in many aqueous solutions, gathers (2-methyl-2-oxazoline) and has the stability that can not compare than polyoxyethylene glycol.In addition starting raw material 2-methyl-2-oxazoline boiling point of synthetic poly-(2-methyl-2-oxazoline) is far above the starting raw material oxyethane of synthesizing polyethylene glycol, and poly-(2-methyl-2-oxazoline) has significantly easily synthetic.Because its good biologically inert, stability and easily synthetic, poly-(2-methyl-2-oxazoline) can become the equivalent material of polyoxyethylene glycol, solves the bad and difficult synthetic problem of polyethylene glycol stabilized property.In method for producing polymer of the present invention, select suitable initiator and chain terminator, various chemical groups can be introduced in chain.Regulate the proportioning of initiator and monomer, can obtain the molecular weight needing.Simultaneously due to this material employing cationoid polymerisation, molecular weight distribution distribution very narrow (PDI<1.2).These characteristics have determined that this material has broad application prospects.
The embodiment of the present invention provides a kind of polymkeric substance, and this polymkeric substance has following chemical structural formula:
Wherein, the random natural number that n is 20-120, R
1for hydrogen atom, methyl or ethyl, R
2for end is with the group of amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base.
Particularly, n is the random natural number in 20-120, for example, 20,, 30,40,45,50,60,76,82,89,92,96,100,110,115,120 etc.; R
1for hydrogen atom, methyl or ethyl, R
2for end is with the group of amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base;
This R
2compound from end with amino, ester group, hydroxyl, sulfydryl, azido-or front three (second) TMOS base.For example:
This end is selected from quadrol, propylene diamine, butanediamine, pentamethylene diamine, hexanediamine etc. with amino compound; Wherein corresponding, R
2as follows:
This end is selected from 4-piperidine carboxylic acid methyl esters, 4-piperidine carboxylate, glycine methyl ester, glycine ethyl ester, 3-alanine methyl esters or 3-alanine ethyl ester etc. with the compound of ester group; Wherein corresponding, R
2as follows:
This end is selected from sodium hydroxide, potassium hydroxide, ethylene glycol with the compound of hydroxyl, propylene glycol, butyleneglycol, pentanediol, hexylene glycol etc.; Wherein corresponding, R
2as follows:
This end is with compound selected from mercapto sodium, 1，2-ethandithiol, Isosorbide-5-Nitrae-succinimide mercaptans or 1, the 6-ethanthiol etc. of sulfydryl; Wherein corresponding, R
2as follows:
This end is selected from sodiumazide or potassium azide with the compound of azido-; Wherein correspondingly, R
2as follows:
N
3。
This end is selected from 3-aminopropyl front three (second) TMOS and 3-sulfydryl front three (second) TMOS etc. with front three (second) oxygen base alkylate; Wherein corresponding, R
2as follows:
Polymkeric substance of the present invention, comprises poly-oxazoline group and ester group or carboxyl and amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base.By this poly-oxazoline group, polymkeric substance of the present invention has very excellent biologically inert, stability and easily synthetic, by this amino, carboxyl, hydroxyl, sulfydryl, azido-or front three (second) TMOS base isoreactivity functional group, make this polymkeric substance crosslinking reaction to occur with the functional group of other character, greatly widened the range of application of this polymkeric substance.
The embodiment of the present invention further provides above-mentioned method for producing polymer, comprises the steps:
Step S01, prepares intermediate product:
2-methyl-2-oxazoline and initiator are added in organic solvent, are to react 6-48 hour under 60-80 ℃ of condition in temperature;
Step S02, introduces end group, purifying:
Temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, by the stirring of removing, add water of solution solvent after reaction, be 9-14 Water Under solution 2-36 hour by the reaction product adding water after stirring in pH value, pH after hydrolysis is adjusted to 6-8, the dry polymkeric substance that obtains of dialysis, described initiator is selected from 3-ethyl bromide or 3-methyl bromide c, and described terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-or front three (second) TMOS base;
Or,
Temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solution solvent part after reaction is removed and obtained thick solution, again solution is added in ether, obtain white suspension liquid, remove supernatant liquid after suspension liquid is centrifugal, after the vacuum-drying of white precipitate product, obtain polymkeric substance.
Or,
Temperature is adjusted to room temperature, by stirrings of removing, add water of solution solvent after reaction, is 9-14 Water Under solution 2-36 hour by the reaction product adding water after stirring in pH value, and rear hydrolysis pH is adjusted to 6-8, and dialysing to be dried obtains polymkeric substance.
In step S01,
This initiator is selected from 3-ethyl bromide or 3-methyl bromide c, and this organic solvent is selected from acetonitrile or dimethyl formamide, and the mol ratio of this initiator and this 2-methyl-2-oxazoline is 0.8-4:100, and the consumption of this organic solvent does not have special requirement.2-methyl-2-oxazoline and initiator are added to after organic solvent, adjust system temperature to 60-80 ℃, reaction 6-48 hour, obtains intermediate product.
In step S02,
This terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-or front three (second) TMOS base.This end with amino compound as quadrol, propylene diamine, butanediamine, hexanediamine etc.; This end with the compound of ester group as 4-piperidine carboxylic acid methyl esters, 4-piperidine carboxylate, glycine methyl ester, glycine ethyl ester, 3-alanine methyl esters, 3-alanine ethyl ester etc.; This end with the compound of hydroxyl as sodium hydroxide, potassium hydroxide, ethylene glycol, propylene glycol, butyleneglycol, pentanediol, hexylene glycol etc.; This end with the compound of sulfydryl as 1，2-ethandithiol, Isosorbide-5-Nitrae-succinimide mercaptans, 1,6-ethanthiol etc.; This end with the compound of azido-as sodiumazide and potassium azide; This end with the compound of front three (second) TMOS base as 3-aminopropyl front three (second) TMOS, 3-hydroxyl front three (second) TMOS, 3-sulfydryl front three (second) TMOS etc.The mol ratio of this terminator and this 2-methyl-2-oxazoline is 1.5-100:100.
In embodiment of the present invention preparation method, the concrete steps of step S02, according to prepared polymkeric substance, can be divided into following three kinds of situations:
The first situation: preparation R
1for hydrogen atom, R
2for end is with the polymkeric substance of amino, carboxyl, hydroxyl (when terminator is not sodium hydroxide and potassium hydroxide), sulfydryl or azido-group, step S02 is specific as follows:
System temperature is adjusted to room temperature, and for example 20-30 ℃ adds terminator in reaction system, then stirs 2-24 hour.Solution after reaction is evaporated under condition of negative pressure, the organic solvent reacting in rear solution is removed, obtain oily thick liquid, in this oily thick liquid, add water, stir, obtain mixing solutions, be 9-14 Water Under solution 2-36 hour by this mixing solutions in pH value, pH after hydrolysis is adjusted to 6-8, the solution of adjusting pH to 6-8 is inserted in dialysis tubing, dialysis in deionized water, dry, obtains polymkeric substance; Wherein this terminator and aforesaid identical, does not repeat to set forth at this.
The second situation: preparation R
1for methyl or ethyl, R
2for end is with the polymkeric substance of amino, hydroxyl (when terminator is not sodium hydroxide and potassium hydroxide), sulfydryl, azido-or front three (second) oxygen base alkyl group, step S02 is specific as follows:
Temperature is adjusted to room temperature, and for example 20-30 ℃, adds terminator, and stirring reaction 2-24 hour removes solution solvent part after reaction to obtain thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtain polymkeric substance.
The third situation: preparation R
1for hydrogen atom, R
2for end is with the polymkeric substance of hydroxyl (when terminator is sodium hydroxide or potassium hydroxide), step S02 is specific as follows:
Temperature is adjusted to room temperature, by the stirring of removing, add water of solution solvent after reaction, be 9-14 Water Under solution 2-36 hour by the reaction product adding water after stirring in pH value, after being hydrolyzed, pH is adjusted to neutrality, as 6-8, obtains mixing solutions, the drying treatment of again this mixing solutions being dialysed, obtains polymkeric substance.
Embodiment of the present invention method for producing polymer, by introducing poly-oxazoline group and other active function groups, realize this bright polymkeric substance and there is very excellent biologically inert, stability and easily synthetic, and can crosslinking reaction occur with the functional group of other character, there is wide range of application.
Below in conjunction with specific embodiment, above-mentioned polymkeric substance and preparation method thereof is described in detail.
Embodiment mono-
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.52mL, 4.0mmol) is joined in reaction system, mixture is heated to 70 ℃ afterwards, react 8 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, add quadrol (6.65mL, 100mmol) to stir 12 hours, under negative pressure, with heating, partial solvent is removed, obtain oily thick liquid, add deionized water to 50mL, the Water Under solution of pH=14 24 hours, pH value of solution is adjusted to neutrality, again the solution that contains polymkeric substance is transferred in dialysis tubing, in deionized water, dialysed 24 hours.Finally, by the solution lyophilize that contains polymkeric substance or decompression heat drying, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 1.8K.
Refer to Fig. 1, Fig. 1 shows the polymkeric substance 1H-nuclear magnetic spectrogram that the embodiment of the present invention is prepared, and as can be seen from Figure 1, the prepared polymkeric substance of above-mentioned preparation method is the compound that said structure formula characterizes.The polymkeric substance that the embodiment of the present invention one is prepared; can introduce a compound (as targeted molecular) that possesses specific function at carboxyl terminal or aminoterminal; and then other nano particles with corresponding functional group or capsule are carried out to chemically modified, to prepare target medicine carrier (as this material of modified with folic acid is connected to target medicine carrier prepared by surface of liposome).In addition this polymkeric substance also can be used for preparing multipolymer (as the multipolymer of the multipolymer of this material and chitosan, this material and PLL, this material and polyacrylic multipolymer etc.).
Embodiment bis-
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.52mL, 4.0mmol) is joined in reaction system, mixture is heated to 70 ℃ afterwards, react 8 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds quadrol (6.65mL, 100mmol) to stir 12 hours, and solution solvent part after reaction is removed and obtained thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 1.9K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention two and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention two is prepared, can be used for preparing multipolymer (as this material and polyacrylic multipolymer).
Embodiment tri-
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0,26mL, 2.0mmol) is joined in reaction system, mixture is heated to 70 ℃ afterwards, react 16 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds 4-piperidine carboxylate (0.92mL, 6.0mmol) to stir 12 hours.Under negative pressure, with heating, partial solvent is removed, obtained oily thick liquid, add deionized water to 50mL, the Water Under solution of pH=14 24 hours, pH value of solution is adjusted to neutrality, then the solution that contains polymkeric substance is transferred in dialysis tubing, in deionized water, dialyse 24 hours.Finally, by the solution lyophilize that contains polymkeric substance or decompression heat drying, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 3,6K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention three and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention three is prepared, can introduce one at a carboxyl terminal and possess the compound (as targeted molecular) of specific function, and then the nano particle with amino or capsule are carried out to chemically modified, to prepare target medicine carrier.In addition, this polymkeric substance also can be used for preparing the hydrogel of tree-like supermolecule polymer or cross-linked network, and for the preparation of multipolymer (as the multipolymer of the multipolymer of this material and chitosan, this material and PLL).
Embodiment tetra-
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.173mL, 1.33mmol) is joined in reaction system, mixture is heated to 70 ℃ afterwards, react 24 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, under negative pressure, with heating, partial solvent is removed, and obtains oily thick liquid.Add deionized water to 50mL, the Water Under solution of pH=14 24 hours, pH value of solution is adjusted to neutrality, then the solution that contains polymkeric substance is transferred in dialysis tubing, in deionized water, dialyse 24 hours.Finally, by the solution lyophilize that contains polymkeric substance or decompression heat drying, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 5.2K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention four and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention four is prepared; can introduce a compound (as targeted molecular) that possesses specific function at the carboxyl terminal of poly-(2-methyl-2-oxazoline) or hydroxyl terminal; and then other nano particles with corresponding functional group or capsule are carried out to chemically modified, to prepare target medicine carrier.In addition this polymkeric substance also can be used for preparing multipolymer (as multipolymer of the multipolymer of the multipolymer of this material and chitosan, this material and PLL, this material and PGA etc.).
Embodiment five
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.173mL, 1.33mmol) is joined in reaction system, mixture is heated to 70 ℃ afterwards, react 24 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds ethylene glycol (2.788mL, 50mmol) to stir 12 hours, and solution solvent part after reaction is removed and obtained thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 5,3K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of inventive embodiments five and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention five is prepared, can be used for preparing multipolymer (as the multipolymer of this material and PGA).
Embodiment six
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.13mL, 1.0mmol) is joined in reaction system, mixture is heated to 75 ℃ afterwards, react 16 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds 1，2-ethandithiol (3.34mL, 40mmol) to stir 12 hours.Under negative pressure, with heating, partial solvent is removed, obtained oily thick liquid.Add deionized water to 50mL, the Water Under solution of pH=14 24 hours, pH value of solution is adjusted to neutrality, then the solution that contains polymkeric substance is transferred in dialysis tubing, in deionized water, dialyse 24 hours.Finally, by the solution lyophilize that contains polymkeric substance or decompression heat drying, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 7.0K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention six and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention six is prepared, can introduce a compound (as targeted molecular) that possesses specific function at the carboxyl terminal of poly-(2-methyl-2-oxazoline), and then gold surface is carried out to chemically modified, to prepare targeted contrast agent or immunology detection chip.In addition can also react with the polymkeric substance that contains unsaturated double-bond by " click " chemistry, to prepare the multipolymer of various uses.
Embodiment seven
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.13mL, 1.0mmol) is joined in reaction system, mixture is heated to 75 ℃ afterwards, react 16 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds 1，2-ethandithiol (3.34mL, 40mmol) to stir 12 hours, and solution solvent part after reaction is removed and obtained thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 7.0K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention seven and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention seven is prepared, can carry out chemically modified to gold surface, to prepare immunology detection chip.In addition can also react with the polymkeric substance that contains unsaturated double-bond by " click " chemistry, to prepare the multipolymer of various uses.
Embodiment eight
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to dimethyl formamide (30mL), then 3-ethyl bromide (0.12mL, 0.92mmol) is joined in reaction system, mixture is heated to 75 ℃ afterwards, react 18 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds sodiumazide (0.40g, 6mmol) to stir 12 hours.Under negative pressure, with heating, partial solvent is removed, obtained oily thick liquid.Add deionized water to 50mL, the Water Under solution of pH=14 24 hours, pH value of solution is adjusted to neutrality, then the solution that contains polymkeric substance is transferred in dialysis tubing, in deionized water, dialyse 24 hours.Finally, by the solution lyophilize that contains polymkeric substance or decompression heat drying, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 8.6K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention eight and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention eight is prepared, can react with the polymkeric substance that contains unsaturated double-bond by " click " chemistry, to prepare the multipolymer of various uses.
Embodiment nine
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to dimethyl formamide (30mL), then 3-ethyl bromide (0.12mL, 0.92mmol) is joined in reaction system, mixture is heated to 75 ℃ afterwards, react 18 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds sodiumazide (0.40g, 6mmol) to stir 12 hours.Solution solvent part after reaction is removed and obtained thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 8.6K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention nine and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention nine is prepared, can react with the polymkeric substance that contains unsaturated double-bond by " click " chemistry, to prepare the multipolymer of various uses
Embodiment ten
The chemical structural formula of embodiment of the present invention polymkeric substance is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
2-methyl-2-oxazoline (8.50mL, 100mmol) is dissolved in to acetonitrile (30mL), then 3-ethyl bromide (0.104mL, 0.800mmol) is joined in reaction system, mixture is heated to 75 ℃ afterwards, react 24 hours;
Stop subsequently heating, thing to be mixed is cooled to room temperature, adds 3-aminopropyl trimethoxysilane (0.70mL, 4.0mmol) to stir 12 hours, and solution solvent part after reaction is removed and obtained thick solution.Again solution is added in ether, obtain white suspension liquid.After suspension liquid is centrifugal, remove supernatant liquid, after the vacuum-drying of white precipitate product, obtaining molecular weight is poly-(2-methyl-2-oxazoline) white solid of 10.5K.
The nuclear magnetic spectrogram of the prepared polymkeric substance of the embodiment of the present invention nine and aforesaid similar, does not repeat to set forth at this.The polymkeric substance that the embodiment of the present invention nine is prepared, can be used for surfaces of various materials to modify (as material surfaces such as gold, glass, silicon-dioxide, silicon rubber, plastics, metal oxides)
This is only preferred embodiment of the present invention above, not in order to limit the present invention, all any modifications of doing within the spirit and principles in the present invention, is equal to and replaces and improvement etc., within all should being included in protection scope of the present invention.
Claims (10)
1. a polymkeric substance, has following chemical structural formula:
Wherein, the random natural number that n is 20-120, R
1for hydrogen atom, methyl or ethyl, R
2for end is with the group of amino, carboxyl, hydroxyl, sulfydryl, azido-, Trimethoxy silane base or triethoxysilicane alkyl.
2. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
3. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
4. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
5. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
6. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
N
3。
7. polymkeric substance as claimed in claim 1, is characterized in that, described R
2for following group:
8. method for producing polymer as claimed in claim 1, comprises the steps:
2-methyl-2-oxazoline and initiator are added in organic solvent, are to react 6-48 hour under 60-80 ℃ of condition in temperature;
Temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, by the stirring of removing, add water of solvent in solution after reaction, be 9-14 Water Under solution 2-36 hour by the reaction product adding water after stirring in pH value, pH after hydrolysis is adjusted to 6-8, the dry polymkeric substance that obtains of dialysis, described initiator is selected from 3-ethyl bromide or 3-methyl bromide c, and described terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-, Trimethoxy silane base or triethoxysilicane alkyl;
Or,
Temperature is adjusted to room temperature, adds terminator, stirring reaction 2-24 hour, removes solution solvent after reaction, adds ether, centrifugal collecting precipitation, and vacuum-drying obtains polymkeric substance; Described terminator is selected from the compound of end with amino, ester group, hydroxyl, sulfydryl, azido-, Trimethoxy silane base or triethoxysilicane alkyl;
Or,
Temperature is adjusted to room temperature, then decompression heating is by stirrings of removing, add water of solution solvent after reaction, is 9-14 Water Under solution 2-36 hour by the reactant adding water after stirring in pH value, and rear hydrolysis pH is adjusted to 6-8, dialysing to be dried obtains polymkeric substance.
9. method for producing polymer as claimed in claim 8, is characterized in that, the mol ratio of described initiator and described 2-methyl-2-oxazoline is 0.8-4:100; The mol ratio of described terminator and described 2-methyl-2-oxazoline is 1.5-100:100.
Polymkeric substance as claimed in claim 1 at nanometer gold image-forming contrast medium, nano-medicament carrier, prepare the application in multipolymer, hydrogel, image-forming contrast medium, material surface modifier.
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| CN110385014A (en) * | 2019-08-02 | 2019-10-29 | 合肥工业大学 | A kind of carbon-dioxide absorbent |
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