CN103626905A - Method for preparing cationic salt response type bottlebrush-shaped polymer - Google Patents
Method for preparing cationic salt response type bottlebrush-shaped polymer Download PDFInfo
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Abstract
The invention relates to a method for preparing a cationic salt response type bottlebrush-shaped polymer. The polymer shows stimulation response depending on ion strength. According to the method, the brush-shaped polymer takes norbornene as a skeleton and a polycaprolactone copolymer containing quaternary ammonium as a side chain, and the polymer is prepared through combining reactions of ring opening metathesis polymerization, ring opening polymerization and click reaction. In water with low ion strength, electrostatic repulsion of cationic quaternary ammonium salt groups causes the brush-shaped macromolecule to dissolve. Along with the addition of salt, the ion strength of the solution gradually increases, the shielding effect of salt ions can convert interaction of quaternary ammonium groups into hydrophobic-hydrophobic interaction, so that the single brush-shaped polymer experiences a stretching state, an agglomeration state and an insoluble state sequentially. The cationic salt response type bottlebrush-shaped polymer has a good potential application prospect in drug delivery, bioengineering, and molecule equipment.
Description
Technical field
The present invention relates to a kind of preparation method of polymkeric substance, relate in particular to a kind of preparation method of cationic salts response type polymer of cleaning bottle brush shape.
Background technology
The nano-scale of cleaning bottle brush shaped polymer and special unit molecule, can have potential applicability at drug delivery, biotechnology and a minute subset.Brush and sac like polymkeric substance contains a linear polymer backbone and highdensity graft side chain conventionally.The synthesis path of brush and sac like polymkeric substance has three kinds: from main chain Graft Method, be grafted to main chain method and large monomer polymerization method; These three kinds of polymerizations respectively have relative merits, and wherein, large monomer polymerization method can have full grafting density and the conforming molecular brush of polymer by controlled polyreaction preparation.Ring-opening metathesis polymerization (ROMP) is a kind of strong polymerization process of preparing the brush and sac like polymkeric substance with controllable molecular weight and narrow molecular weight distributions.
The conformation of the physicals of response type polymer, especially macromolecular chain, can be affected by the stimulation of outside (as pH, temperature, optical, electrical environment, redox environment and magnetic field etc.).As a rule, small environmental change will cause the violent variation of this base polymer conformation or other performance, as other response type polymer, molecular brush also can be designed to respond to the polymkeric substance of outside stimulus, because molecular brush is single molecule, the motivating force of the conformational change of induction outside stimulus is special often, but also has peculiar advantage simultaneously.For example, the responsiveness unit molecule bundle of molecular brush can be used as controlled packing and the release of medicine.Micelle-forming concentration, for the formation of ampholyte copolymer, must be avoided the too early release of medicine, but for single molecular beam, does not but have this problem.
In response type molecular brush, the molecular brush research of salt response type seldom.The micella of ionic segmented copolymer, because being subject to the control of micelle-forming concentration, causes stability very low; Under the moisture state of high ionic strength, it is insoluble that the ionic charge of polymkeric substance can be masked the therefore molecular chain of polymkeric substance by salt in water, thereby provides intensity for product; On the other hand, thus it is to be solublely convenient to it and to be cleaned that electrostatic repulsion forces makes again these polymer molecules in water or in the water of low ionic strength.
Summary of the invention
The present invention relates to a kind of degradable cationic cleaning bottle brush shaped polymer, this base polymer has shown very strong salt responsiveness.
The present invention relates to a kind of preparation method of cationic salts response type polymer of cleaning bottle brush shape.
A preparation method for the cationic salts response type polymer of cleaning bottle brush shape, its step is as follows:
(1) N-[3-hydroxypropyl]-cis-5-norbornylene-outer-2, synthesizing of 3-dicarboximide (NPH): cis-5-norbornylene-outer-2,3-dicarboxylic anhydride (NDA) (2.0g, 8.0mmol) be dissolved into 20mL methylene dichloride (DCM), 3-amino-1-propyl alcohol (0.80g, 8.4mmol) under magnetic agitation, dropwise splash in dichloromethane solution, then solvent evaporates the mixture obtaining and is dried 12～18h at 120～130 ℃, and final mixture obtains NPH by aluminum cylinder.
(2) ethyl-dimethyl-propargyl bromination ammonium is synthetic: 2-methylamino-1-propine (10.00g, 120.2mmol) join in the round-bottomed flask that contains 30mL tetrahydrofuran (THF) (THF), add again 1-bromic ether (7.90g, 72.2mmol), reaction mixture was 35 ℃ of stirring reactions 2 days, then solvent and excessive bromic ether evaporate, the mixture obtaining is washed three times to remove unnecessary 3-dimethylamino-1-propine with diethyl etherate, and Quaternary ammonium bromide is finally dry in vacuum drying oven.
(3) NPH-PCL-block-P (α Cl ε CL) (α-chloro-ε-acyl ester in oneself) macromonomer is prepared in ring-opening polymerization: NPH-PCL-block-P (α Cl ε CL) macromonomer with different polymerization degree is prepared by ring-opening polymerization; ε CL (0.91g, 8.0mmol) and α Cl ε CL (0.30g, 2.0mmol) are dissolved in the toluene that 1mL is dry and then join in the reaction flask that fills NPH initiator (0.044g, 0.2mmol), obtain mixture N
2advertise 10min.Under nitrogen protection, by Sn (OCt)
2(0.008g; 0.02mmol) be dissolved in the toluene that 0.2mL is dry and then transfer in reaction flask; final reaction mixture in nitrogen protection at 110 ℃ stirring reaction 24h; after reaction; by mixture cool to room temperature; by dilution with toluene, precipitate twice in cooling methyl alcohol, then vacuum-drying 24h until weight no longer change.
(4) ring-opening metathesis polymerization is prepared PNPH-grafting-[PCL-block-P (α Cl ε CL)] molecular brush: in a reaction flask that is full of nitrogen, macromonomer NPH-grafting-[PCL-block-P (α Cl ε CL)] (400mg, 61,5 μ mol) be dissolved in the toluene that 5mL is dry; Reaction flask seals solid nitrogen purge 15min, under nitrogen protection gas, add a kind of GrubbsIII of containing catalyzer (0.9mg, 1.23 μ mol) 2mL degassed toluene solution, after the 60 ℃ of stirring 4h of mixture that obtain, add 1mL ethyl vinyl ether to stop polyreaction, solution continues to stir 30min and is then deposited in excessive methyl alcohol; Polymkeric substance is separated final vacuum by the method for filtering and is dried until weight no longer changes.
(5) PNPH-grafting-[PCL-block-P (α N
3cL)] molecular brush is synthetic: PNPH-grafting-[PCL-block-P (α Cl ε CL)] (0.4g, 0.65mmol α Cl ε CL) is dissolved in DMF (DMF); Then add mixture that sodium azide (0.21g, 3.25mmol) obtains at stirring at room 24h, after reaction, solid leaches, and DMF reduction vaporization falls, and the mixture obtaining is dissolved in toluene, and undissolved solid is centrifugal falls (5000rpm; 15min); Finally, multipolymer obtains by the mode of underpressure distillation again.
(6) prepare PNPH-grafting-[PCL-block-P (CL-grafting-quaternary ammonium salt)] molecular brush: PNPH-grafting-[PCL-block-P (α N
3ε CL)] (0.22g, 0.36mmol α N3 ε CL) and EDPQA (0.076g, 0.40mmol) join in the round-bottomed flask that contains DMF, the mixture obtaining nitrogen purge 10min; Then join dry 4h at 35 ℃, mixture that DBU (0.0055g, 0.036mmol) and CuI (0.0068g, 0.036mmol) obtain; After reaction, multipolymer precipitates then vacuum-drying at cold diethyl etherate, and the dissolution of solid leaching is removed remaining small molecules and other impurity to the 6h that then dialyses in water, and final multipolymer obtains by lyophilize.
The present invention has prepared a kind of polymkeric substance of cationic cleaning bottle brush shape, this polymkeric substance demonstrates the stimulating responsive that depends on ionic strength, the polymkeric substance of brush and sac like is usingd norbornylene as skeleton, the polycaprolactam ester copolymer that contains quaternary ammonium is as side chain, prepared by the association reaction by ring-opening metathesis polymerization, ring-opening polymerization and click-reaction, in the water of low ionic strength, the Coulomb repulsion between cationic quaternary ammonium salt groups can be dissolved brush and sac like polymer.Along with adding of salt, the ionic strength of solution increases gradually, therefore the shielding effect of salt ion can change the interaction between quaternary ammonium group into hydrophobic-hydrophobic interaction, and can to experience from unfolding state-transition be that aggregating state finally becomes insoluble state to single brush and sac like polymkeric substance.
Embodiment
In order to deepen the understanding of the present invention, below in conjunction with specific examples, the present invention is described further.
(1) N-[3-hydroxypropyl]-cis-5-norbornylene-outer-2, synthesizing of 3-dicarboximide (NPH): cis-5-norbornylene-outer-2,3-dicarboxylic anhydride (NDA) (2.0g, 8.0mmol) be dissolved into 20mL methylene dichloride (DCM), 3-amino-1-propyl alcohol (0.80g, 8.4mmol) under magnetic agitation, dropwise splash in dichloromethane solution, then solvent evaporates the mixture that obtains at 120 ℃ of dry 15h, and final mixture obtains NPH by aluminum cylinder.
(2) ethyl-dimethyl-propargyl bromination ammonium is synthetic: 2-methylamino-1-propine (10.00g, 120.2mmol) join in the round-bottomed flask that contains 30mL tetrahydrofuran (THF) (THF), add again 1-bromic ether (7.90g, 72.2mmol), reaction mixture was 35 ℃ of stirring reactions 2 days; Then solvent and excessive bromic ether evaporate, and the mixture obtaining is washed three times to remove unnecessary 3-dimethylamino-1-propine with diethyl etherate, and Quaternary ammonium bromide is finally dry in vacuum drying oven.
(3) NPH-PCL-block-P (α Cl ε CL) (α-chloro-ε-acyl ester in oneself) macromonomer is prepared in ring-opening polymerization: NPH-PCL-block-P (α Cl ε CL) macromonomer with different polymerization degree is prepared by ring-opening polymerization; ε CL (0.91g, 8.0mmol) and α Cl ε CL (0.30g, 2.0mmol) are dissolved in the toluene that 1mL is dry and then join in the reaction flask that fills NPH initiator (0.044g, 0.2mmol), obtain mixture N
2advertise 10min, under nitrogen protection, by Sn (OCt)
2(0.008g, 0.02mmol) is dissolved in the toluene that 0.2mL is dry and then transfers in reaction flask; Final reaction mixture in nitrogen protection at 110 ℃ stirring reaction 24h, after reaction, by mixture cool to room temperature, by dilution with toluene, precipitate twice in cooling methyl alcohol, then vacuum-drying 24h until weight no longer change.
(4) ring-opening metathesis polymerization is prepared PNPH-grafting-[PCL-block-P (α Cl ε CL)] molecular brush: in a reaction flask that is full of nitrogen, macromonomer NPH-grafting-[PCL-block-P (α Cl ε CL)] (400mg, 61,5 μ mol) be dissolved in the toluene that 5mL is dry; Reaction flask seals solid nitrogen purge 15min, under nitrogen protection gas, add a kind of GrubbsIII of containing catalyzer (0.9mg, 1.23 μ μ mol) 2mL degassed toluene solution, adds 1mL ethyl vinyl ether to stop polyreaction after the 60 ℃ of stirring 4h of mixture that obtain; Solution continues to stir 30min and is then deposited in excessive methyl alcohol, and polymkeric substance is separated final vacuum by the method for filtering and is dried until weight no longer changes.
(5) PNPH-grafting-[PCL-block-P (α N
3cL)] molecular brush is synthetic: PNPH-grafting-[PCL-block-P (α Cl ε CL)] (0.4g, 0.65mmol α Cl ε CL) is dissolved in DMF (DMF); Then add mixture that sodium azide (0.21g, 3.25mmol) obtains at stirring at room 24h, after reaction, solid leaches, and DMF reduction vaporization falls; The mixture obtaining is dissolved in toluene, and undissolved solid is centrifugal falls (5000rpm; 15min), last, multipolymer obtains by the mode of underpressure distillation again.
(6) prepare PNPH-grafting-[PCL-block-P (CL-grafting-quaternary ammonium salt)] molecular brush: PNPH-grafting-[PCL-block-P (α N
3ε CL)] (0.22g, 0.36mmol α N3 ε CL) and EDPQA (0.076g, 0.40mmol) join in the round-bottomed flask that contains DMF, the mixture obtaining nitrogen purge 10min; Then join DBU (0.0055g, 0.036mmol) and CuI (0.0068g, dry 4h at 35 ℃, the mixture that 0.036mmol) obtains, after reaction, multipolymer precipitates then vacuum-drying at cold diethyl etherate, and the dissolution of solid leaching is removed remaining small molecules and other impurity to the 6h that then dialyses in water.The multipolymer finally obtaining obtains by lyophilize.
Claims (1)
1. a preparation method for the cationic salts response type polymer of cleaning bottle brush shape, its step is as follows:
(1) N-[3-hydroxypropyl]-cis-5-norbornylene-outer-2,3-dicarboximide (NPH) synthetic:
Cis-5-norbornylene-outer-2,3-dicarboxylic anhydride (NDA) (2.0g, 8.0mmol) be dissolved into 20mL methylene dichloride (DCM), 3-amino-1-propyl alcohol (0.80g, 8.4mmol) under magnetic agitation, dropwise splash in dichloromethane solution, then solvent evaporates the mixture obtaining and is dried 12～18h at 120～130 ℃, and final mixture obtains NPH by aluminum cylinder;
(2) ethyl-dimethyl-propargyl bromination ammonium is synthetic:
2-methylamino-1-propine (10.00g, 120.2mmol) join in the round-bottomed flask that contains 30mL tetrahydrofuran (THF) (THF), add again 1-bromic ether (7.90g, 72.2mmol), reaction mixture was 35 ℃ of stirring reactions 2 days, the mixture obtaining is washed three times to remove unnecessary 3-dimethylamino-1-propine with diethyl etherate, and Quaternary ammonium bromide is finally dry in vacuum drying oven;
(3) NPH-PCL-block-P (α Cl ε CL) (α-chloro-ε-acyl ester in oneself) macromonomer is prepared in ring-opening polymerization: NPH-PCL-block-P (α Cl ε CL) macromonomer with different polymerization degree is prepared by ring-opening polymerization, ε CL (0.91g, 8.0mmol) with α Cl ε CL (0.30g, 2.0mmol) be dissolved in the toluene that 1mL is dry and then join and fill NPH initiator (0.044g, in reaction flask 0.2mmol), obtain mixture N
2advertise 10min, under nitrogen protection, by Sn (OCt)
2(0.008g, 0.02mmol) be dissolved in the toluene that 0.2mL is dry and then transfer in reaction flask, final reaction mixture in nitrogen protection at 110 ℃ stirring reaction 24h, after reaction, by mixture cool to room temperature, by dilution with toluene, precipitate twice in cooling methyl alcohol, then vacuum-drying 24h until weight no longer change;
(4) ring-opening metathesis polymerization is prepared PNPH-grafting-[PCL-block-P (α Cl ε CL)] molecular brush:
In a reaction flask that is full of nitrogen, macromonomer NPH-grafting-[PCL-block-P (α Cl ε CL)] (400mg, 61.5 μ mol) be dissolved in the toluene that 5mL is dry, reaction flask seals solid nitrogen purge 15min, under nitrogen protection gas, add a kind of GrubbsIII of containing catalyzer (0.9mg, 1.23 μ μ mol) 2mL degassed toluene solution, after the 60 ℃ of stirring 4h of mixture that obtain, add 1mL ethyl vinyl ether to stop polyreaction, solution continues to stir 30min and is then deposited in excessive methyl alcohol, polymkeric substance is separated final vacuum by the method for filtering and is dried until weight no longer changes,
(5) PNPH-grafting-[PCL-block-P (α N
3cL)] molecular brush is synthetic:
PNPH-grafting-[PCL-block-P (α Cl ε CL)] (0.4g, 0.65mmol α Cl ε CL) be dissolved into N, in dinethylformamide (DMF), then add mixture that sodium azide (0.21g, 3.25mmol) obtains at stirring at room 24h, after reaction, solid leaches, DMF reduction vaporization falls, and the mixture obtaining is dissolved in toluene, and undissolved solid is centrifugal falls (5000rpm; 15min), last, multipolymer obtains by the mode of underpressure distillation again;
(6) prepare PNPH-grafting-[PCL-block-P (CL-grafting-quaternary ammonium salt)] molecular brush: PNPH-grafting-[PCL-block-P (α N
3ε CL)] (0.22g, 0.36mmol α N3 ε CL) and EDPQA (0.076g, 0.40mmol) join in the round-bottomed flask that contains DMF, the mixture obtaining nitrogen purge 10min, then join DBU (0.0055g, 0.036mmol) and CuI (0.0068g, dry 4h at 35 ℃, the mixture that 0.036mmol) obtains, after reaction, multipolymer precipitates then vacuum-drying at cold diethyl etherate, the dissolution of solid leaching is removed remaining small molecules and other impurity to the 6h that then dialyses in water, and final multipolymer obtains by lyophilize.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110016111A (en) * | 2018-01-08 | 2019-07-16 | 天津大学 | It is a kind of based on the self assembly object and its synthetic method of brush block polymer and application |
| CN113754506A (en) * | 2021-10-13 | 2021-12-07 | 西南科技大学 | Nano core-shell combustion catalyst and preparation method thereof |
-
2013
- 2013-11-15 CN CN201310586337.0A patent/CN103626905A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| KEJIAN YAO ET AL: ""Cationic Salt-Responsive Bottle-Brush Polymers"", 《MACROMOLECULAR RAPID COMMUNICATIONS》 * |
| 刘超等: ""由活性开环聚合反应和紫外光辐照法合成功能性环状聚(ε-己内酯-co-α-氯代-ε-己内酯)"", 《2013年全国高分子学术论文报告会论文摘要集--主题A：高分子合成》 * |
| 孔立智等: ""通过大分子单体的"点击"反应合成超支化聚苯乙烯"", 《高分子通报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110016111A (en) * | 2018-01-08 | 2019-07-16 | 天津大学 | It is a kind of based on the self assembly object and its synthetic method of brush block polymer and application |
| CN110016111B (en) * | 2018-01-08 | 2021-08-13 | 天津大学 | Self-assembly based on brush-shaped block polymer and synthesis method and application thereof |
| CN113754506A (en) * | 2021-10-13 | 2021-12-07 | 西南科技大学 | Nano core-shell combustion catalyst and preparation method thereof |
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Application publication date: 20140312 |