CN102775530A - RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative - Google Patents
RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative Download PDFInfo
- Publication number
- CN102775530A CN102775530A CN2012101720871A CN201210172087A CN102775530A CN 102775530 A CN102775530 A CN 102775530A CN 2012101720871 A CN2012101720871 A CN 2012101720871A CN 201210172087 A CN201210172087 A CN 201210172087A CN 102775530 A CN102775530 A CN 102775530A
- Authority
- CN
- China
- Prior art keywords
- phema
- lysine
- multipolymer
- preparation
- boc
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 CCCC(C)(C(C)(C)NC(NC(C)(C)N)=N)C(OCCO*)=* Chemical compound CCCC(C)(C(C)(C)NC(NC(C)(C)N)=N)C(OCCO*)=* 0.000 description 1
Images
Abstract
The invention provides an RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative, belonging to the technical field of functional material. The preparation method comprises the following steps of: taking hydroxyethyl methacrylate (HEMA) and lysine (L-lysine) as raw materials, taking trithiocarbonate as a chain transfer agent, sequentially adopting a reversible addition fragmentation chain transfer (RAFT) free radical polymerization method to obtain PHEMA homopolymer with different chain segment lengths, wherein the molecular weight of the PHEMA homopolymer is controllable, and obtaining PHEM-co-PHEMA-Boc-L-lysine copolymer by an esterification. The preparation method is simple, the prepared PHEM-co-PHEMA-L-lysine copolymer has biocompatibility, the composite formed by the electrostatic interaction between the PHEM-co-PHEMA-L-lysine copolymer and the plasmid DNA (pDNA) can be widely applicable to the fields such as the drug slow-release system, the gene therapy and the like.
Description
Technical field
A kind of RAFT preparation method of polylysine verivate belongs to technical field of function materials.
Background technology
Along with the development and the application of new technology, various new macromolecular material is a dark horse, and plays the important and pivotal role in people's productive life field.Yet in the quality that brings convenience to people's lives, makes the life better at macromolecular material, a large amount of wastes after it uses also grow with each passing day, and the environment of depending on for existence to the mankind has caused very important negative impact.The used monomer Rocryl 400 (HEMA) of the present invention is environmentally friendly raw material, and Methionin (L-lysine) is the amino acid of needed by human body, has caused the extensive concern of researcher about the research of preparation, structure and the performance of their multipolymers.Wherein, Rocryl 400 (HEMA) is very important monomer, is a kind of hydrophilic polymer by HEMA synthetic PHEMA, and water regain can reach 40% of own wt.Hydroxyl is the very strong polar group of adsorptivity in the polymkeric substance, also is reactive group, is prone to react, and as the copolymerization component of vinyl resin, gives the polymkeric substance wetting ability, improves cementability, also can play crosslinked action through hydroxyl reaction.Because of having hydroxyl possess hydrophilic property and excellent biocompatibility.Main medical macromolecular materials as ophthalmology and dentistry are main raws of making contact lense at present.PHEMA is rising medical macromolecular materials.Methionin (L-lysine) is the amino acid of needed by human body; A kind of as in the polyamino acid of polylysine, since 1975, researchs such as Laemmli showed that PLL has the ability of parcel DNA; Polylysine is just because the main chain configuration of its line style polypeptide; Degradable is the Methionin of needed by human body in vivo, and excellent biological compatibility and be easy to carry out plurality of advantages such as chemically modified becomes maximum one type of research in the cationic polymers.Carry out at present in the research of polylysine, the mode of seldom useful radical polymerization obtains the research of the verivate of polylysine.And the polymkeric substance that traditional radical polymerization obtains is because to polymer architecture; Molecular weight and distribution controlled bad; Burden ability to DNA when cytotoxicity that the high-molecular weight polylysine causes and lower molecular weight is not good, makes particularly important to the control of polymer architecture.The present invention utilizes the method for RAFT (RAFT) radical polymerization; The molecular weight of the homopolymer of preparation PHEMA and distribution thereof can realize through proportioning and the polymerization reaction time of regulating monomer, initiator and chain-transfer agent; Obtain the PHEMA-co-PHEMA-Boc-L-lysine multipolymer through esterification; Obtain the PHEMA-co-PHEMA-L-lysine multipolymer through deprotection and have excellent biological compatibility, can be used as bio-medical material and be widely used in fields such as medicament slow release system and gene therapy.
Summary of the invention
The RAFT preparation method who the purpose of this invention is to provide a kind of polylysine verivate.
Technical scheme of the present invention: a kind of RAFT preparation method of polylysine verivate; Being directly to adopt trithiocarbonate is chain-transfer agent; With Rocryl 400 (HEMA), Methionin (L-lysine) is raw material; Adopt the RAFT free radical polymerisation process earlier, the homopolymer of preparation poly hydroxy ethyl acrylate (PHEMA) obtains the PHEMA-co-PHEMA-Boc-L-lysine multipolymer through esterification then.(TFA) carries out deprotection to multipolymer through trifluoroacetic acid, obtains the PHEMA-co-PHEMA-L-lysine multipolymer.This multipolymer can form the PHEMA-co-PHEMA-L-lysine/pDNA mixture through electrostatic interaction and DNA (pDNA).
The proportioning of homopolymer PHEMA is: monomer 1 (HEMA): the mol ratio of trithiocarbonate: AIBN is 100: 3: 1, adopts solution polymerization, and solvent is the trimethyl carbinol, and consumption is 3 times of amount of monomer, in 75 ℃ of reaction 5h, and frozen water cooling stopped reaction; With cold diethyl ether product is precipitated three times, dry under 30 ℃ at last, get white product.
The proportioning of PHEMA-co-PHEMA-Boc-L-lysine multipolymer is: monomer 2 (Boc-L-lysine): poly hydroxy ethyl acrylate (PHEMA): the mol ratio of DCC: DMAP is 1: 1.5: 1.3: 0.6, and use DMF to be solvent.
Take by weighing monomer 2, PHEMA, DCC and DMAP by proportioning and place reactor drum, add a certain amount of anhydrous ethyl acetate, in 25 ℃ of reaction 24h.After reaction finished, underpressure distillation removed and desolvates, and deposition is three times in ether, gets light yellow solid.
The method for preparing the PHEMA-co-PHEMA-L-lysine multipolymer is: the PHEMA-co-PHEMA-Boc-L-lysine multipolymer is dissolved in a certain amount of methylene dichloride, to middle adding trifluoroacetic acid, stirs 12h under the room temperature, with the anhydrous diethyl ether deposition, obtain product.
Characterize through the structure and the performance of characterizing methods such as Fourier transform infrared spectroscopy, nucleus magnetic resonance, gel permeation chromatography, transmission electron microscope to homopolymer and multipolymer, the result shows that polymer architecture is clear and definite.
Beneficial effect of the present invention: PHEMA-co-PHEMA-L-lysine multipolymer prepared according to the methods of the invention has excellent biocompatibility; The molecular weight of polymkeric substance can be realized through regulating feed ratio and polymerization reaction time; This multipolymer is with a wide range of applications in fields such as drug sustained release system, gene therapies as biocompatible materials.
Description of drawings
The nuclear magnetic spectrogram of Fig. 1 homopolymer PHEMA.
The nuclear magnetic spectrogram of Fig. 2 copolymer p HEMA-co-PHEMA-Boc-L-lysine.
Embodiment
Embodiment 1
Take by weighing Rocryl 400 (HEMA) 1.00g (7.684 * 10
-3Mol), trithiocarbonate 0.0839g (2.305 * 10
-4Mol), AIBN0.0128g (7.684 * 10
-5Mol), trimethyl carbinol 4ml adds in the 50ml reactor drum, logical nitrogen 30min protection before the reaction; Under magnetic agitation, be warming up to 75 ℃, behind the reaction 5h, frozen water cooling stopped reaction precipitates three times with cold diethyl ether; Obtain homopolymer PHEMA at 30 ℃ of following freeze-day with constant temperature then, product is a white, molecular weight M
N (GPC)=5.4 * 10
4, MWD is 1.52.
Embodiment 2
Take by weighing Methionin (Boc-L-lysine) 1.010g (2.15 * 10 of Boc protection
-2Mol), PHEMA0.38g (7.6 * 10
-6Mol), DCC 0.793g (3.84 * 10
-3Mol), DMAP 0.0202g (1.65 * 10
-4Mol), DMF15ml adds in the 50ml reactor drum, under magnetic agitation, maintains the temperature at 25 ℃, and behind the reaction 24h, underpressure distillation removes and desolvates, and in ether, precipitates, and gets the PHEMA-co-PHEMA-Boc-L-lysine multipolymer, and product is light yellow.
Claims (5)
1. the RAFT preparation method of a polylysine verivate belongs to technical field of function materials.The present invention is a raw material with Rocryl 400 (HEMA), Methionin (L-lysine); Trithiocarbonate is a chain-transfer agent; Adopt RAFT (RAFT) free radical polymerisation process to obtain having the PHEMA homopolymer of different chain lengths earlier, obtain the PHEMA-co-PHEMA-Boc-L-lysine multipolymer through esterification then.Utilize trifluoroacetic acid (TFA) that multipolymer is carried out deprotection, obtain the PHEMA-co-PHEMA-L-lysine multipolymer.The molecular weight of homopolymer is controlled, and this PHEMA-co-PHEMA-L-lysine multipolymer can be compound with DNA (pDNA), forms mixture.
The proportioning of preparation PHEMA homopolymer is: monomer (HEMA): trithiocarbonate: the mol ratio of azo-bis-isobutyl cyanide (AIBN) is 100: 3: 1, adopts solution polymerization, in 75 ℃ of reaction 5h, and frozen water cooling stopped reaction; With cold diethyl ether product is precipitated three times, dry under 30 ℃ at last, get white product.
The mole proportioning of preparation PHEMA-co-PHEMA-Boc-L-lysine multipolymer is: monomer 2 (Boc-L-lysine): gather methyl-prop diluted acid hydroxyl ethyl ester (PHEMA): dicyclohexyl carbon imide (DCC): 4-dimethylaminopyridine (DMAP)=1: 1.5: 1.3: 0.6; Solvent is N, dinethylformamide (DMF).
Take by weighing monomer 2, PHEMA, DCC and DMAP by proportioning and place reactor drum, in 25 ℃ of reaction 24h.After reaction finished, underpressure distillation removed and desolvates, and deposition is three times in ether, gets light yellow solid.
The method for preparing the PHEMA-co-PHEMA-L-lysine multipolymer is: the PHEMA-co-PHEMA-Boc-L-lysine multipolymer is dissolved in a certain amount of methylene dichloride, to middle adding trifluoroacetic acid, stirs 12h under the room temperature, with the anhydrous diethyl ether deposition, obtain product.
2. solution polymerization method according to claim 1, gained PHEMA homopolymer is:
Be expressed as PHEMA.
3. the PHEMA-co-PHEMA-Boc-L-lysine multipolymer that preparation method according to claim 1 makes is:
Be expressed as PHEMA-co-PHEMA-Boc-L-lysine.
4. the PHEMA-co-PHEMA-L-lysine multipolymer that preparation method according to claim 1 makes is:
Be expressed as PHEMA-co-PHEMA-L-lysine, this multipolymer has biocompatibility.
5. the PHEMA-co-PHEMA-L-lysine multipolymer that preparation method according to claim 1 makes can synthesize the PHEMA-co-PHEMA-L-lysine/pDNA mixture with plasmid dna complex.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101720871A CN102775530A (en) | 2012-05-30 | 2012-05-30 | RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101720871A CN102775530A (en) | 2012-05-30 | 2012-05-30 | RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102775530A true CN102775530A (en) | 2012-11-14 |
Family
ID=47120657
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101720871A Pending CN102775530A (en) | 2012-05-30 | 2012-05-30 | RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102775530A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011473A (en) * | 2016-11-14 | 2017-08-04 | 天津大学 | Leucine methyl Voncoat R 3310 and preparation method and the application in antibacterial |
| CN107011472A (en) * | 2016-11-14 | 2017-08-04 | 天津大学 | Application of the controllable living polymerization in regulation and control leucine-lysine methacrylate copolymer is chiral |
| CN108070062A (en) * | 2016-11-14 | 2018-05-25 | 天津大学 | D- cationic chiral amino acid methacrylate copolymers and preparation and antibacterial applications |
| CN108070045A (en) * | 2016-11-14 | 2018-05-25 | 天津大学 | L- cationic chiral amino acid methacrylate copolymers and preparation and antibacterial applications |
| CN109796549A (en) * | 2016-11-14 | 2019-05-24 | 天津大学 | The preparation method of lysine methacrylate homopolymer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101792496A (en) * | 2010-01-29 | 2010-08-04 | 武汉理工大学 | Method for preparing gradient copolymer |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
-
2012
- 2012-05-30 CN CN2012101720871A patent/CN102775530A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101792496A (en) * | 2010-01-29 | 2010-08-04 | 武汉理工大学 | Method for preparing gradient copolymer |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011473A (en) * | 2016-11-14 | 2017-08-04 | 天津大学 | Leucine methyl Voncoat R 3310 and preparation method and the application in antibacterial |
| CN107011472A (en) * | 2016-11-14 | 2017-08-04 | 天津大学 | Application of the controllable living polymerization in regulation and control leucine-lysine methacrylate copolymer is chiral |
| CN108070062A (en) * | 2016-11-14 | 2018-05-25 | 天津大学 | D- cationic chiral amino acid methacrylate copolymers and preparation and antibacterial applications |
| CN108070045A (en) * | 2016-11-14 | 2018-05-25 | 天津大学 | L- cationic chiral amino acid methacrylate copolymers and preparation and antibacterial applications |
| CN109796549A (en) * | 2016-11-14 | 2019-05-24 | 天津大学 | The preparation method of lysine methacrylate homopolymer |
| CN107011472B (en) * | 2016-11-14 | 2019-09-13 | 天津大学 | Application of the controllable living polymerization in regulation leucine-lysine methacrylate copolymer chirality |
| CN108070062B (en) * | 2016-11-14 | 2019-10-25 | 天津大学 | D- cationic chiral amino acid methacrylate copolymer and preparation and antibacterial applications |
| CN107011473B (en) * | 2016-11-14 | 2019-10-25 | 天津大学 | Leucine methyl Voncoat R 3310 and preparation method and the application in antibacterial |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107550921B (en) | Nanoparticle-polymer injectable composite hydrogel double-drug-loading system and preparation method thereof | |
| CN102775530A (en) | RAFT (reversible addition fragmentation chain transfer) preparation method of polylysine derivative | |
| CN103087333B (en) | Preparation method of quick dissociative type thermosensitive hyaluronic acid hydrogel | |
| CN101716346B (en) | Supramolecular hydrogel gene vector material, and preparation method and application thereof | |
| CN102718991A (en) | High strength injectable hydrogel and preparation method thereof | |
| CN102093555B (en) | Polymer nano hydrogel and preparation method thereof | |
| Yuan et al. | Cationic peptide-based salt-responsive antibacterial hydrogel dressings for wound healing | |
| CN101696272A (en) | Degradable material having multiple sensitive properties, manufacturing method thereof and use thereof | |
| CN106632949A (en) | Oligochitosan or derivative-modified polyurethane fiber dressing and preparation method thereof | |
| CN103467728B (en) | A kind of degradable amphoteric ion polymer with Bioconjugate and preparation method thereof | |
| CN102851304A (en) | Electrostatic coating based non-viral nucleic acid ternary complex system and preparation method thereof | |
| CN104892917B (en) | Glucosamine-modified polyethyleneglycol-polylactic acid, preparation method therefor and application thereof | |
| Zhao et al. | Rapidly thermoreversible and biodegradable polypeptide hydrogels with sol–gel–sol transition dependent on subtle manipulation of side groups | |
| CN102408560B (en) | Preparation method of environment response type radial copolymer | |
| CN102391429A (en) | PH-sensitive xylan hydrogel and preparation method thereof | |
| CN102924653B (en) | Poly (N- isopropyl acrylamide)- poly (crylic acid or acrylic acid derivative) copolymer and preparation method thereof | |
| CN101235384B (en) | Method for preparing non-virus cation type gene vector | |
| CN102526810B (en) | Artificial skin alternative material and preparation method thereof | |
| CN100365043C (en) | Synthesis of ABA polypeptide -b- polytetrahydrofuran-b-polypeptide triblock copolymer | |
| CN101565497A (en) | Amphiphilic block copolymer, nano-particles thereof and method for preparing same | |
| CN104311820B (en) | A kind of method that degradable medicaments carrier is built based on polysaccharide graft poly-aspartate benzyl ester | |
| CN101450996A (en) | Glucose responding type polyphosphazene hydrogel and preparation method thereof | |
| CN101717496B (en) | Copolymer of fibroin and poly L-lactic acid, preparation method thereof through ring-opening polymerization and application thereof | |
| CN115073769A (en) | Active oxygen response supramolecular hydrogel for promoting tissue regeneration and preparation method thereof | |
| CN101445606B (en) | Copolymer of fibroin and poly L-lactic acid, melt polymerization preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121114 |