CN108935513A - A kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver and preparation method - Google Patents
A kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver and preparation method Download PDFInfo
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- C08F2438/03—Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX]
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Abstract
The present invention relates to a kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver and preparation methods; using 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid as RAFT polymerizable chain transfer agents; using 2- ((tert-butoxycarbonyl) amino) ethyl ester as monomer; azodiisobutyronitrile is initiator; it obtains poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) containing three thioester groups after being polymerize by RAFT, sloughs tert-butoxycarbonyl and protect to obtain poly- (2- aminoethylacrylate).Coordination reduction can occur with silver ion for amido abundant on polymer chain, and it is poly- (2- aminoethylacrylate) to prepare stable load silver.It is 20~30% that silver carrying amount, which accounts for its mass percent, assigns its excellent antibacterial activity.Meanwhile still containing three thioester groups in this polymer macromolecule chain, it can be used as Macromolecular chain transfer agent and participate in and prepare block copolymer in the polymerization of second comonomer.
Description
Technical field
The invention belongs to synthesis of polymer material fields, are related to a kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver
And preparation method, it is related to functional load silver-colored poly- (2- aminoethylacrylate) and preparation method.
Background technique
The generation of multi-drug resistant bacterium, so that exploitation safety and efficient antibacterials are imperative, metallic silver conduct
Antibacterial agent has wide spectrum, potent, lasting, the characteristics of having no drug resistance, and design and synthesis organic polymer is combined with metallic silver
Antibacterial agent improves biocompatibility while guaranteeing antibacterial activity, is that silver is applied as antibacterial primitive in field of biomedicine
Effective means.
" Guangyu Zhang, Feng Zhang, Hideaki Morikawa, the Yueyue Chen et of document 1
al.One-step synthesis of silver nanoparticles in an aqueous solution and
Their antibacterial activities.Appl Phys A (2014) 114:1277-1283 " discloses a kind of water-soluble
The method of one-step synthesis method carrying silver antimicrobials in liquid uses amino-terminated dissaving polymer as stabilizer in synthesis
And reducing agent, but its biocompatibility is not studied, it is limited in the application of biomedical aspect.
Document 2 " Zhiqiang Zhang, Ramesh C.Patel, Rajshree Kothari, Colin P.Johnson,
and Stig E.Friberg et al.Stable Silver Clusters and Nanoparticles Prepared in
Polyacrylate and Inverse Micellar Solutions.J.Phys.Chem.B 2000,104,1176-1182”
One kind is disclosed in the presence of polyacrylate ion, prepares silver nano-grain with sodium borohydride reduction silver nitrate in aqueous solution
Method, this method needs to use sodium borohydride as reducing agent, not simple and convenient enough.
Document 3 be " Li Guoping, Luo Yunjun, the silver ion such as thick ability of Xu and polyamidoamine tree form modification coordination
Chinese Journal of Inorganic Chemistry is studied, 2003.11,1212-1216 ", which is disclosed, a kind of prepares different types of polyamidoamine
(PAMAM) tree form modification and Ag+Coordination, the method for generating complex, but obtained tree form modification are easy to happen intermolecular
Crosslinking, limit it in the application of field of biomedicine.
Summary of the invention
Technical problems to be solved
In order to avoid the shortcomings of the prior art, the present invention proposes that a kind of load silver-colored poly- (2- aminoethylacrylate) is anti-
Microbial inoculum and preparation method.
Technical solution
Poly- (2- aminoethylacrylate) antibacterial agent of a kind of load silver, it is characterised in that prepare component are as follows: different with azo two
Butyronitrile: 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid: the molar ratio of 2- ((tert-butoxycarbonyl) amino) ethyl ester is
1:3.2~4.5:32~40 obtain poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) that the degree of polymerization is 12~15；To slough uncle
Poly- (2- aminoethylacrylate) after butoxy carbonyl protection, which reacts to obtain with silver nitrate molar ratio 1:12~18, carries silver-colored gather
(2- aminoethylacrylate) antibacterial agent；In poly- (2- aminoethylacrylate) antibacterial agent of obtained load silver: silver carrying amount accounts for
Its gross weight is 20%~30%, and the molar ratio of monomer 2- aminoethylacrylate and silver is 1.3~1.5:1 on polymer chain,
The grafting rate of silver is up to 65%~75%.
A method of it preparing poly- (2- aminoethylacrylate) antibacterial agent of load silver, feature described in claim 1 and exists
In steps are as follows:
Step 1: under condition of ice bath, in molar ratio 1:1.2~1.8:2.5~3.5 by N- (tertiary butyl oxycarbonyl) ethanol amine,
Acryloyl chloride and triethylamine mixing after be dissolved in dry tetrahydrofuran, continue ice bath 3h~5h after, be stirred at room temperature reaction 20~
30h；After completion of the reaction, the hydrochloride for removing triethylamine complexing is filtered, is dissolved in chloroform after rotary evaporation concentration with saturation
Sodium bicarbonate solution extraction is washed 3 times, and extraction is washed gained lower liquid anhydrous sodium sulfate and removes water drying, rotary evaporation is by clear solution
Concentration crosses silicagel column, filtrate is taken, after Rotary Evaporators solvent evaporated using n-hexane-ethyl acetate blend solution as eluant, eluent
White solid is obtained to polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used；
Step 2: azodiisobutyronitrile, 2- is added in 1:3.2~4.5:32~40 in molar ratio in dry Schlenk pipe
(((dodecylthio) thiocarbonyl) is thio) propionic acid and 2- ((tert-butoxycarbonyl) amino) ethyl ester, with dry Isosorbide-5-Nitrae-dioxy
Six rings remove the dissolved oxygen in reaction tube with Schlenk technology after being completely dissolved as solvent；Then sealing stirring is in 65~75
10~14h is reacted under the conditions of DEG C；After reaction, system is exposed in air and is cooled to room temperature, then by product in ice
Precipitated in n-hexane, stand 2~4h after remove supernatant, then be dried under vacuum to constant weight at room temperature, obtain yellow solid i.e.
For poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) of the protection of end group tert-butoxycarbonyl；
Step 3: the poly- (2- for the end group tert-butoxycarbonyl protection that step 2 obtains being added into dry single-necked flask
((tert-butoxycarbonyl) amino) ethyl ester), and n,N-Dimethylformamide and distilled water volume is added than the blend solution for 1:1
As solvent；The trifluoroacetic acid for being 10~15 times with poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) mass ratio is then added；
Then 24~36h is stirred to react at 30~40 DEG C；To which after reaction, vacuum distillation removes part distilled water and trifluoro second
Acid, be reloaded into molecular cut off be 300D bag filter at room temperature pure water dialyse 48~56h, obtain sloughing uncle after freeze-drying
Poly- (the 2- aminoethylacrylate) of butoxy carbonyl protection；
Step 4: under the conditions of being protected from light, poly- (the 2- amino second that molar ratio is 1:12~18 being added into dry single-necked flask
Base acrylate) and silver nitrate, pure water is added and is used as solvent, is completely dissolved dissolved oxygen in rear Bubbling method removing solution, at system
Sealed under nitrogen atmosphere it is intact after be protected from light 20 in room temperature~for 24 hours；To which after reaction, loading molecular cut off is 300D
Bag filter under the conditions of room temperature is protected from light pure water dialyse 36~48h, it is living with antibacterial that dark brown solid is obtained after freeze-drying
The load silver of property is poly- (2- aminoethylacrylate).
The Schlenk technology is: after reactant and solvent to be added to dry Schlenk pipe, first with liquid nitrogen frozen with
Afterwards, in a nitrogen atmosphere, it vacuumizes, then is passed through nitrogen, then liquid nitrogen frozen again, in this way freeze-thaw-refrigeration operation repeatedly
Repeatedly.
The ice n-hexane of the step 2 is: n-hexane being placed in -18 DEG C~-22 DEG C freezer compartment of refrigerator and places 30min~1h
Gained afterwards.
The step 4 be protected from light condition refer to aluminium foil by reaction vessel package be protected from light.
The Bubbling method of the step 4 refers to: after dry single-necked flask is added in reactant and solvent, will be connected with nitrogen
Under clean syringe needle insertion flask liquid level, leads to 15~30min of nitrogen, remove oxygen in solution.
The solvent that tetrahydrofuran, the 1,4- dioxane solvent of the drying are plus 5A molecular sieve is dry.
The step 2 is heated to be with solution described in step 3 to be carried out under the conditions of constant temperature oil bath.
Beneficial effect
A kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver proposed by the present invention and preparation method, using 2-
(((dodecylthio) thiocarbonyl) is thio) propionic acid is as RAFT polymerizable chain transfer agents, with 2- ((tert-butoxycarbonyl) amino)
Ethyl ester is monomer, and azodiisobutyronitrile is initiator, is obtained after being polymerize by RAFT containing poly- (2- ((the tertiary fourth oxygen of three thioester groups
Base carbonyl) amino) ethyl ester), slough tert-butoxycarbonyl and protect to obtain poly- (2- aminoethylacrylate).It is rich on polymer chain
Coordination reduction can occur with silver ion for rich amido, and it is poly- (2- aminoethylacrylate) to prepare stable load silver.It carries
It is 20~30% that silver content, which accounts for its mass percent, assigns its excellent antibacterial activity.Meanwhile in this polymer macromolecule chain still
So contain three thioester groups, can be used as Macromolecular chain transfer agent and participate in and prepare block copolymer in the polymerization of second comonomer.
Detailed description of the invention
Fig. 1: the nuclear magnetic spectrogram of poly- (the 2- aminoethylacrylate) of the method for the present invention preparation
Fig. 2: (2- aminoethylacrylate) poly- prepared by the method for the present invention and poly- (2- amino-ethyl propylene after silver is carried
Acid esters) thermal weight loss map
Fig. 3: after the prepared load silver poly- (2- aminoethylacrylate) of the method for the present invention implementation acts on Escherichia coli
The ne ar observed with scanning electron microscope
Fig. 4: the method for the present invention implements prepared load silver poly- (2- aminoethylacrylate) and is acting on mammal just
The histogram of the cell survival rate obtained after normal cell
Specific embodiment
Now in conjunction with embodiment, attached drawing, the invention will be further described:
Steps are as follows for the preparation method of poly- (2- aminoethylacrylate) antibacterial agent of load silver:
Step a: under condition of ice bath, in molar ratio 1:1.2~1.8:2.5~3.5 by N- (tertiary butyl oxycarbonyl) ethanol amine,
Acryloyl chloride, triethylamine mixing after be dissolved in dry tetrahydrofuran, continue ice bath 3h~5h after, be stirred at room temperature reaction 20~
30h；After completion of the reaction, the hydrochloride for removing triethylamine complexing is filtered, is dissolved in chloroform after rotary evaporation concentration with saturation
Sodium bicarbonate solution extraction is washed 2~3 times, and organic phase anhydrous sodium sulfate is removed water drying, and clear solution is concentrated rotary evaporation, with
Ethyl acetate: n-hexane is that the blend solution of 1:6~10 is eluant, eluent, crosses silicagel column, filtrate is taken, with Rotary Evaporators solvent evaporated
After obtain white solid, as polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used.
Step b: azodiisobutyronitrile, 2- is added in 1:3.2~4.5:32~40 in molar ratio in dry Schlenk pipe
(((dodecylthio) thiocarbonyl) is thio) propionic acid, 2- ((tert-butoxycarbonyl) amino) ethyl ester, with dry Isosorbide-5-Nitrae-dioxy
Six rings remove the dissolved oxygen in reaction tube with Schlenk technology after being completely dissolved as solvent；Then sealing stirring is in 65~75
10~14h is reacted under the conditions of DEG C；After reaction, system is exposed in air and is cooled to room temperature, then by product in ice
Precipitated in n-hexane, stand 2~4h after remove supernatant, then be dried under vacuum to constant weight at room temperature, obtain yellow solid i.e.
For poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) of the protection of end group tert-butoxycarbonyl.
Step c: the poly- (2- for the end group tert-butoxycarbonyl protection that step 2 obtains is added into dry single-necked flask
((tert-butoxycarbonyl) amino) ethyl ester), and n,N-Dimethylformamide and distilled water volume is added than being total to for 1:1~1.5
Miscible fluid is as solvent；The trifluoro for being 10~15 times with poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) mass ratio is then added
Acetic acid；Then 24~36h is stirred to react at 30~40 DEG C；To which after reaction, vacuum distillation removes part distilled water and three
Fluoroacetic acid, be reloaded into molecular cut off be 100D~500D bag filter at room temperature pure water dialyse 48~56h, after freeze-drying
Obtain sloughing poly- (the 2- aminoethylacrylate) of tert-butoxycarbonyl protection.
Step d: under the conditions of being protected from light, poly- (the 2- amino second that molar ratio is 1:12~18 is added into dry single-necked flask
Base acrylate) and silver nitrate, pure water is added and is used as solvent, is completely dissolved dissolved oxygen in rear Bubbling method removing solution, at system
Sealed under nitrogen atmosphere it is intact after be protected from light 20 in room temperature~for 24 hours；To which after reaction, loading molecular cut off is 300D
The bag filter of~500D under the conditions of room temperature is protected from light pure water dialyse 36~48h, obtained after freeze-drying dark brown solid be with
The load silver of antibacterial activity is poly- (2- aminoethylacrylate).
Embodiment one:
It weighs N- (tertiary butyl oxycarbonyl) ethanol amine 1.61g to be placed in the dry single-necked flask of 50ml, it is dry that 10ml is added
Tetrahydrofuran, 5.5ml triethylamine is added after ice bath stirring 20min, 1.21ml acryloyl chloride is dissolved in 5ml tetrahydrofuran solution
In, it is slowly dropped in flask with syringe, system is sealed after being added dropwise and continues ice bath 4h, ice bath is removed and is stirred at room temperature instead
Should the hydrochloride for removing triethylamine complexing be filtered, is dissolved in chloroform after rotary evaporation concentration with full for 24 hours, after completion of the reaction
It is washed 3 times with sodium bicarbonate solution extraction, organic phase anhydrous sodium sulfate is removed water into drying, clear solution is concentrated rotary evaporation, with
N-hexane: ethyl acetate volume ratio 8:1 blend solution is eluant, eluent, crosses silicagel column, filtrate is taken, with Rotary Evaporators solvent evaporated
After obtain white solid 1.71g, as polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used.
Into dry Schlenk pipe be added 70mg 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid,
Isosorbide-5-Nitrae-dioxy of the drying of 5ml is added in 387.2mg 2- ((tert-butoxycarbonyl) amino) ethyl ester, 8.2mg azodiisobutyronitrile
Six rings are as solvent, after above-mentioned substance is dissolved, under Schlenk technical conditions, with vacuumizing after liquid nitrogen frozen, then up
It states and leads to nitrogen about 30s in system, again by solution liquid nitrogen frozen, repeatedly three times, then sealing stirring is reacted in 70 DEG C
12h.After reaction, system is exposed in air and is cooled to room temperature, after product is then precipitated 2h in ice n-hexane
Supernatant is removed, is dried under vacuum to constant weight at 30 DEG C, obtaining 290mg yellow solid is what end group tert-butoxycarbonyl was protected
Poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester).
It weighs 260mg poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) to be placed in the dry single-necked flask of 25ml, be added
The n,N-Dimethylformamide of 5ml and 5ml distilled water are used as solvent, then addition 3ml trifluoroacetic acid, after sealing at 35 DEG C magnetic
Power is stirred to react for 24 hours.After reaction, molecular cut off is packed into after removing part distilled water and trifluoroacetic acid with Rotary Evaporators
For the bag filter of 300D, pure water is dialysed 48~56h at room temperature, obtains sloughing the poly- of tert-butoxycarbonyl protection after freeze-drying
(2- aminoethylacrylate).
Weigh poly- (2- aminoethylacrylate) 100mg, silver nitrate 80mg be placed in aluminium foil package 25ml beaker in, add
Enter 10ml pure water as solution, Bubbling method removes dissolved oxygen in solution, system be under nitrogen atmosphere seal it is intact after in room temperature
Reaction is for 24 hours.To after reaction, be packed into bag filter that molecular cut off is 300D under the conditions of room temperature is protected from light pure water dialysis 36~
48h obtains having the load silver of antibacterial activity poly- (2- aminoethylacrylate) after freeze-drying.
It can be seen that poly- (2- aminoethylacrylate) result prepared by the present embodiment from the nuclear magnetic spectrogram of Fig. 1 to produce
Object is consistent with designed expection product structure, and nuclear-magnetism integral show that the degree of polymerization is 12~15.
The hot weightless picture of poly- (2- aminoethylacrylate) after poly- (the 2- aminoethylacrylate) and load silver of Fig. 2
Spectrum is it can be easily seen that it is 22%~25% that silver carrying amount, which accounts for its gross weight,.
The ne ar observed from Fig. 3 scanning electron microscope can be seen that load is silver-colored poly- (2- aminoethylacrylate)
After acting on Escherichia coli, bacterium occur surface shrinkage, rupture, fusion phenomena such as illustrate that bacterium is killed by antibacterial agent.
Silver-colored poly- (2- aminoethylacrylate) is carried as can be seen from Figure 4 act on after mammal normal cell obtain
Cell survival rate is up to 94%, illustrates that the biocompatibility of synthetic product is good.
Embodiment two:
It weighs N- (tertiary butyl oxycarbonyl) ethanol amine 2.42g to be placed in the dry single-necked flask of 100ml, it is dry that 15ml is added
Tetrahydrofuran, 8.25ml triethylamine is added after ice bath stirring 20min, it is molten that 1.82ml acryloyl chloride is dissolved in 7.5ml tetrahydrofuran
It in liquid, is slowly dropped in flask with syringe, system is sealed after being added dropwise and continues ice bath 4h, ice bath is removed and is stirred at room temperature
Reaction for 24 hours, after completion of the reaction, filters the hydrochloride for removing triethylamine complexing, is dissolved in chloroform and using after rotary evaporation concentration
Saturated sodium bicarbonate solution extraction is washed 3 times, and organic phase anhydrous sodium sulfate is removed water drying, and clear solution is concentrated rotary evaporation,
Using n-hexane: ethyl acetate volume ratio 8:1 blend solution crosses silicagel column, takes filtrate, be evaporated with Rotary Evaporators molten as eluant, eluent
White solid 2.63g is obtained after agent, as polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used.
Into dry Schlenk pipe be added 70mg 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid,
Isosorbide-5-Nitrae-dioxy of the drying of 5ml is added in 387.2mg 2- ((tert-butoxycarbonyl) amino) ethyl ester, 8.2mg azodiisobutyronitrile
Six rings are as solvent, after above-mentioned substance is dissolved, under Schlenk technical conditions, with vacuumizing after liquid nitrogen frozen, then up
It states and leads to nitrogen about 30s in system, again by solution liquid nitrogen frozen, repeatedly three times, then sealing stirring is reacted in 70 DEG C
12h.After reaction, system is exposed in air and is cooled to room temperature, after product is then precipitated 2h in ice n-hexane
Supernatant is removed, is dried under vacuum to constant weight at 30 DEG C, obtaining 275mg yellow solid is what end group tert-butoxycarbonyl was protected
Poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester).
It weighs 390mg poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) to be placed in the dry single-necked flask of 50ml, be added
As solvent 4.5ml trifluoroacetic acid is then added, 35 after sealing in the n,N-Dimethylformamide and 7.5ml distilled water of 7.5ml
Magnetic agitation is reacted for 24 hours at DEG C.After reaction, retention is packed into after removing part distilled water and trifluoroacetic acid with Rotary Evaporators
The bag filter that molecular weight is 300D at room temperature dialyse 48~56h by pure water, obtains sloughing tert-butoxycarbonyl guarantor after freeze-drying
Poly- (the 2- aminoethylacrylate) of shield.
Weigh poly- (2- aminoethylacrylate) 150mg, silver nitrate 120mg be placed in aluminium foil package 25ml beaker in,
Be added 12ml pure water be used as solution, Bubbling method removing solution in dissolved oxygen, system be under nitrogen atmosphere seal it is intact after in room
Temperature reaction is for 24 hours.To after reaction, be packed into bag filter pure water dialysis 36 under the conditions of room temperature is protected from light that molecular cut off is 300D
~48h obtains having the load silver of antibacterial activity poly- (2- aminoethylacrylate) after freeze-drying.
Embodiment three:
It weighs N- (tertiary butyl oxycarbonyl) ethanol amine 3.22g to be placed in the dry single-necked flask of 100ml, it is dry that 20ml is added
Tetrahydrofuran, 11ml triethylamine is added after ice bath stirring 20min, 2.42ml acryloyl chloride is dissolved in 10ml tetrahydrofuran solution
In, it is slowly dropped in flask with syringe, system is sealed after being added dropwise and continues ice bath 4h, ice bath is removed and is stirred at room temperature instead
Should the hydrochloride for removing triethylamine complexing be filtered, is dissolved in chloroform after rotary evaporation concentration with full for 24 hours, after completion of the reaction
It is washed 3 times with sodium bicarbonate solution extraction, organic phase anhydrous sodium sulfate is removed water into drying, clear solution is concentrated rotary evaporation, with
N-hexane: ethyl acetate volume ratio 8:1 blend solution is eluant, eluent, crosses silicagel column, filtrate is taken, with Rotary Evaporators solvent evaporated
After obtain white solid 3.52g, as polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used.
Into dry Schlenk pipe be added 70mg 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid,
Isosorbide-5-Nitrae-dioxy of the drying of 5ml is added in 387.2mg 2- ((tert-butoxycarbonyl) amino) ethyl ester, 8.2mg azodiisobutyronitrile
Six rings are as solvent, after above-mentioned substance is dissolved, under Schlenk technical conditions, with vacuumizing after liquid nitrogen frozen, then up
It states and leads to nitrogen about 30s in system, again by solution liquid nitrogen frozen, repeatedly three times, then sealing stirring is reacted in 70 DEG C
12h.After reaction, system is exposed in air and is cooled to room temperature, after product is then precipitated 2h in ice n-hexane
Supernatant is removed, is dried under vacuum to constant weight at 30 DEG C, obtaining 283mg yellow solid is what end group tert-butoxycarbonyl was protected
Poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester).
It weighs 520mg poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) to be placed in the dry single-necked flask of 50ml, be added
As solvent 6ml trifluoroacetic acid is then added, after sealing at 35 DEG C in the n,N-Dimethylformamide and 10ml distilled water of 10ml
Magnetic agitation is reacted for 24 hours.After reaction, retention molecule is packed into after removing part distilled water and trifluoroacetic acid with Rotary Evaporators
The bag filter for being 30D 48~56h of pure water dialysis at room temperature is measured, obtains sloughing the poly- of tert-butoxycarbonyl protection after freeze-drying
(2- aminoethylacrylate).
Weigh poly- (2- aminoethylacrylate) 300mg, silver nitrate 240mg be placed in aluminium foil package 50ml beaker in,
Be added 25ml pure water be used as solution, Bubbling method removing solution in dissolved oxygen, system be under nitrogen atmosphere seal it is intact after in room
Temperature reaction is for 24 hours.To after reaction, be packed into bag filter pure water dialysis 36 under the conditions of room temperature is protected from light that molecular cut off is 300D
~48h obtains having the load silver of antibacterial activity poly- (2- aminoethylacrylate) after freeze-drying.
Claims (8)
1. a kind of poly- (2- aminoethylacrylate) antibacterial agent of load silver, it is characterised in that prepare component are as follows: with two isobutyl of azo
Nitrile: 2- (((dodecylthio) thiocarbonyl) is thio) propionic acid: the molar ratio of 2- ((tert-butoxycarbonyl) amino) ethyl ester is 1:
3.2~4.5:32~40 obtain poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) that the degree of polymerization is 12~15；To slough tertiary fourth
Poly- (2- aminoethylacrylate) after Epoxide carbonyl protection reacts to obtain the poly- (2- of load silver with silver nitrate molar ratio 1:12~18
Aminoethylacrylate) antibacterial agent；In poly- (2- aminoethylacrylate) antibacterial agent of obtained load silver: it is total that silver carrying amount accounts for it
Weight is 20%~30%, and the molar ratio of monomer 2- aminoethylacrylate and silver is 1.3~1.5:1 on polymer chain, silver-colored
Grafting rate is up to 65%~75%.
2. a kind of method for preparing poly- (2- aminoethylacrylate) antibacterial agent of load silver described in claim 1, it is characterised in that
Steps are as follows:
Step 1: under condition of ice bath, 1:1.2~1.8:2.5~3.5 are by N- (tertiary butyl oxycarbonyl) ethanol amine, propylene in molar ratio
It is dissolved in dry tetrahydrofuran after acyl chlorides and triethylamine mixing, after continuing ice bath 3h~5h, 20~30h of reaction is stirred at room temperature；
After completion of the reaction, the hydrochloride for removing triethylamine complexing is filtered, is dissolved in chloroform after rotary evaporation concentration and uses unsaturated carbonate
Hydrogen sodium solution extraction is washed 3 times, and extraction is washed gained lower liquid anhydrous sodium sulfate and removes water drying, rotary evaporation is dense by clear solution
Contracting crosses silicagel column, takes filtrate using n-hexane-ethyl acetate blend solution as eluant, eluent, is obtained with after Rotary Evaporators solvent evaporated
It is to polymerize monomer 2- ((tert-butoxycarbonyl) amino) ethyl ester used to white solid；
Step 2: azodiisobutyronitrile, 2- (((ten is added in 1:3.2~4.5:32~40 in molar ratio in dry Schlenk pipe
Two alkylthio groups) thiocarbonyl) thio) propionic acid and 2- ((tert-butoxycarbonyl) amino) ethyl ester, with dry Isosorbide-5-Nitrae-dioxane
As solvent, the dissolved oxygen in reaction tube is removed with Schlenk technology after being completely dissolved；Then sealing stirring is in 65~75 DEG C of items
10~14h is reacted under part；After reaction, system exposure in air and is cooled to room temperature, then by product ice just oneself
Precipitated in alkane, stand 2~4h after remove supernatant, then be dried under vacuum to constant weight at room temperature, obtain yellow solid be end
Poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) of base tert-butoxycarbonyl protection；
Step 3: poly- (2- ((the tertiary fourth for the end group tert-butoxycarbonyl protection that step 2 obtains being added into dry single-necked flask
Epoxide carbonyl) amino) ethyl ester), and n,N-Dimethylformamide and distilled water volume is added than the blend solution for 1:1 as molten
Agent；The trifluoroacetic acid for being 10~15 times with poly- (2- ((tert-butoxycarbonyl) amino) ethyl ester) mass ratio is then added；Then exist
24~36h is stirred to react at 30~40 DEG C；To which after reaction, vacuum distillation removing part distilled water and trifluoroacetic acid refill
Enter molecular cut off be 300D bag filter at room temperature pure water dialyse 48~56h, obtain sloughing tert-butoxy after freeze-drying
Poly- (the 2- aminoethylacrylate) of carbonyl-protection；
Step 4: under the conditions of being protected from light, poly- (the 2- amino-ethyl third that molar ratio is 1:12~18 being added into dry single-necked flask
Olefin(e) acid ester) and silver nitrate, pure water is added as solvent, is completely dissolved rear Bubbling method and removes dissolved oxygen in solution, system is in nitrogen
Atmosphere enclose lower sealing it is intact after be protected from light 20 in room temperature~for 24 hours；It is the saturating of 300D to after reaction, be packed into molecular cut off
Bag 36~48h of pure water dialysis under the conditions of room temperature is protected from light is analysed, it is with antibacterial activity that dark brown solid is obtained after freeze-drying
Carry silver-colored poly- (2- aminoethylacrylate).
3. method according to claim 2, it is characterised in that: the Schlenk technology is: reactant and solvent being added dry
It after dry Schlenk pipe, first with after liquid nitrogen frozen, in a nitrogen atmosphere, vacuumizes, then be passed through nitrogen, then liquid nitrogen again
Freezing, freeze-thaw-refrigeration operation is multiple repeatedly in this way.
4. method according to claim 2, it is characterised in that: the ice n-hexane of the step 2 is: n-hexane is placed in -18
DEG C~-22 DEG C of freezer compartment of refrigerator place gained after 30min~1h.
5. method according to claim 2, it is characterised in that: the step 4 be protected from light condition refer to aluminium foil will reaction hold
Device package is protected from light.
6. method according to claim 2, it is characterised in that: the Bubbling method of the step 4 refers to: reactant and solvent are added
After entering dry single-necked flask, it will be connected under the clean syringe needle insertion flask liquid level of nitrogen, lead to 15~30min of nitrogen, remove molten
Oxygen in liquid.
7. method according to claim 2, it is characterised in that: tetrahydrofuran, the Isosorbide-5-Nitrae-dioxane solvent of the drying be
The solvent for adding 5A molecular sieve dry.
8. method according to claim 2, it is characterised in that: solution described in the step 2 and step 3 is heated to be in thermostatical oil
It is carried out under the conditions of bath.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111909364A (en) * | 2020-08-11 | 2020-11-10 | 常州美胜生物材料有限公司 | Preparation method of silver-series antibacterial masterbatch |
| CN115486444A (en) * | 2022-09-21 | 2022-12-20 | 河北省科学院能源研究所 | Preparation method of silver-loaded polymer vesicle |
| CN115671298A (en) * | 2022-11-21 | 2023-02-03 | 温州医科大学 | ROS (reactive oxygen species) -responsive antibacterial drug nano-carrier and preparation method thereof |
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2018
- 2018-07-16 CN CN201810774468.4A patent/CN108935513B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111909364A (en) * | 2020-08-11 | 2020-11-10 | 常州美胜生物材料有限公司 | Preparation method of silver-series antibacterial masterbatch |
| CN111909364B (en) * | 2020-08-11 | 2022-05-17 | 常州美胜生物材料有限公司 | Preparation method of silver-series antibacterial masterbatch |
| CN115486444A (en) * | 2022-09-21 | 2022-12-20 | 河北省科学院能源研究所 | Preparation method of silver-loaded polymer vesicle |
| CN115486444B (en) * | 2022-09-21 | 2024-01-30 | 河北省科学院能源研究所 | Preparation method of silver-loaded polymer vesicle |
| CN115671298A (en) * | 2022-11-21 | 2023-02-03 | 温州医科大学 | ROS (reactive oxygen species) -responsive antibacterial drug nano-carrier and preparation method thereof |
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