CN108285537A - A kind of fluorine-containing nonionic surfactant of amide bond and its preparation method and application - Google Patents
A kind of fluorine-containing nonionic surfactant of amide bond and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to fluorine-containing nonionic surfactants of a kind of amide bond and its preparation method and application.The surfactant such as formula（Ⅰ）It is shown：Wherein, it be 8 ~ 130, y is 12 ~ 75 that m, which is 25 ~ 80, x+z,.The fluorine-containing nonionic surfactant of amide bond provided by the invention is obtained by the reaction by carboxylic acid perfluor polytrimethylene ether and specific hydrophilic ammonia based compound by amide, with good bio-compatibility and stability, purity is high, can be widely used in the IVC of in vitro culture field.In addition, the product purity and yield that preparation method provided by the invention is prepared are high, it is simple for process.
Description
Technical field
The invention belongs to surfactant fields, and in particular to a kind of fluorine-containing nonionic surfactant of amide bond and
Preparation method and application.
Background technology
The hydrogen atom in hydrocarbon chain in conventional surfactants molecule is replaced partly or completely with fluorine atom, just at
For fluorinated surfactant.The peculiar property of fluorinated surfactant is related with the property of fluorine atom and carbon-fluorine bond.It is primarily due to fluorine original
Son is the highest element of electronegativity, so the bond energy of carbon-fluorine bond is very high.Secondly, the atomic radius ratio hydrogen of covalent bond and fluorine atom is former
Sub is big, and more effectively fluoridized C-C key protections can be got up.Therefore, fc-surfactant has very high heat steady
Qualitative and chemical stability.Also, fc-surfactant is also with the irreplaceable particularity of many hc-surfactants
Can --- " three high " " two hate ".
The micro-fluidic sharpest edges for being widely used in the fields in vitro culture IVC of drop are that can largely to generate size equal
One emulsion droplet.In IVC in application, the experiment needs on biology are hatched in drop, and need a certain specific
At a temperature of carry out.However, the thermodynamic phase of drop introduces some problems to IVC applications.Therefore, in two-phase system
Surfactant plays the role of key.In IVC applications, surfactant must be stable to drop first.It is assembled in
Surface active molecules at two-phase interface can reduce the interfacial tension of two-phase, prevent the fusion between drop.Secondly, surface is lived
Property agent must be biologically inert, can the inner surface of water droplet formed a biologically inert inner surface, will not be to the life in water phase
Object ingredient damages.Finally, surfactant must also be nonionic surfactant, otherwise can with DNA/RNA, albumen or
Electrostatic interaction occurs for the opposite charges in other biological molecule.In addition, IVC is in application, the oil-based liquid with biological non-toxicity
Compare less, and again simultaneously meet good permeability, should hydrophobicity the good liquid of lipophobia is just more rare again.Often
This class I liquid I is typically chosen the solvent containing carbon fluorine chain, and the interfacial tension of these this provinces of carbon fluorocarbon oil is much lower compared with water.This
More harsh requirement is just proposed to surfactant.Need to find a kind of surfactant to balance drop stability and life
The fluorinated surfactant of dynamic equilibrium between object compatibility, nonionic is exactly ideal selection, not only hydrophobic but also lipophobic.
Currently, surfactant used is perfluor polytrimethylene ether carboxylate, carboxylic acid ion carries charge, can be big with biology
Certain electrostatic interaction occurs for molecule so that the function of large biological molecule is damaged.Therefore, in order to solve this problem,
Perfluor polytrimethylene ether and uncharged hydrophilic polymer obtain total block as the block copolymer of polyethylene glycol carries out covalent bond
Polymer.These total block polymers at normal temperatures play the stability of drop very crucial effect.But when certain
At specific temperature, the thermal stability for the drop that block polymer is stablized is total to regard to far short of what is expected by these.For example, with temperature
Raising, solubility of the polyethylene glycol section in carbon fluorocarbon oil just reduces very much, its thermal stability is caused to be deteriorated.So finding
The application in biology micro-fluidic to drop of bio-compatibility surfactant with thermal stability is very crucial.
Therefore, a kind of surfactant with thermal stability and bio-compatible of exploitation with important research significance and is answered
With value.
Invention content
It is an object of the invention to overcome the difference of perfluoropolyether nonionic surfactant thermal stability in the prior art
Defect provides a kind of fluorine-containing nonionic surfactant of amide bond.Surfactant provided by the invention is by carboxylic acid perfluor
Polytrimethylene ether is obtained by the reaction with specific hydrophilic ammonia based compound by amide, has good bio-compatibility and stability,
It can be widely used in the IVC of in vitro culture field.
Another object of the present invention is to provide the preparation methods of above-mentioned surfactant.
Another object of the present invention is to provide the applications in above-mentioned surfactant in vitro culture field.
For achieving the above object, the present invention adopts the following technical scheme that：
A kind of fluorine-containing nonionic surfactant of amide bond, the surfactant such as formula（Ⅰ）It is shown：
Wherein, it be 8 ~ 130, y is 12 ~ 75 that m, which is 25 ~ 80, x+z,.
Surfactant provided by the invention is Perfluoropolyether amide compound nonionic surfactant.Existing perfluor
Carboxylic acid perfluor polytrimethylene ether and different types of hydrophilic amino of the Polyetheramide compounds nonionic surfactant by long-chain
It closes object to be made by amidation process, such as the EA surfactants that business procurement is arrived（Raindance, the U.S.）, Pico-
Surf™（Dolomite, Britain）Deng.But the commercially produced product of these surfactants is not pure single substance, and
It is to be dissolved in carbon fluorocarbon oil with specific concentration, cannot be satisfied and the concentration of pure material and surfactant is wanted under specific condition
It asks, especially in biologic applications, including PCR reactions must avoid interference of the impurity to reaction.In addition, hydrophilic ammonia based compound by
Amination in itself is unstable and is difficult to store（Such as double amino-polyethyleneglycols NH2-PEG-NH2）, so must now buy existing
With, higher price, and entire preparation process is restricted.Therefore, the selection of hydrophilic ammonia based compound is to influence perfluoropolyether
An important factor for performance of amide compound nonionic surfactant, should consider hydrophilic amino chemical combination when choosing
Influence of the object to the thermal stability and bio-compatibility of final surfactant considers its difficulty or ease journey for obtaining and storing again
Degree, it is also contemplated that the purity and price of finally obtained surface-active.
The present inventor has found after repeatedly screening, when the formula of selection（Ⅴ）Shown Amino End Group compound：
When, obtained surfactant has preferable bio-compatibility and stabilization
Property.The reason is that, the Amino End Group compound is triblock copolymer, pass through the value for choosing suitable x, y and z so that its
There is preferable solubility and thermostabilization under specific temperature conditions.In addition, surfactant provided by the invention is with higher pure
Degree, can be widely used in the IVC of in vitro culture field.
X can be 0 or other suitable integer in the present invention；Y in the present invention can be 0 or other suitable integer
Preferably, m is 25 ~ 45；X+z is that 12 ~ 90, y is 15 ~ 60.
It is further preferable that m is 45；X+z is 60, y 42.
Preferably, the average molecular weight of the surfactant is 16000 ~ 23000.
It is further preferable that the average molecular weight of the surfactant is 17000 ~ 23000.
The preparation method of above-mentioned fluorine-containing nonionic surfactant, includes the following steps：
S1：By formula（Ⅱ）Shown carboxylic acid perfluor polytrimethylene ether chloride, obtains formula（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides；
S2：By formula（Ⅳ）It is formula using hydrazine hydrate reduction after shown terminal hydroxy group compound sulfonylation（Ⅴ）Shown Amino End Group chemical combination
Object；
S3：Formula（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides and formula（Ⅴ）Shown Amino End Group compound carries out amide and reacts up to the table
Face activating agent.
The present invention passes through to formula（Ⅱ）Shown carboxylic acid perfluor polytrimethylene ether chloride, substantially increases entire amidation process
Activity so that the product that preparation method of the invention obtains not only yield higher, and also quality is more preferable.
In addition, the present invention selects particular hydrophilic amino-compound by formula（Ⅳ）Shown terminal hydroxy group compound：Polypropylene glycol-
The triblock copolymer of block-polyethylene glycol-block-polypropylene glycol converts to obtain, the triblock polymer itself be it is a kind of not
The nonionic surfactant of electrification, and by the value of specific x, y and z, there is preferable solubility and thermal stability；Separately
Outside, hydrophilic ammonia based compound is prepared by it to can avoid unstable existing for the hydrophilic ammonia based compound directly selected being difficult to store up
The problem of depositing into and influencing finally obtained surfactant properties, so that the surfactant being prepared has preferably
Thermal stability and bio-compatibility, and yield is high, and purity is high.
The present invention provides a kind of method of specific chloride, it is preferable that the process of chloride is in S1：By formula（Ⅱ）Institute
Show that carboxylic acid perfluor polytrimethylene ether is dissolved in solvent, in N2Under atmosphere, the acyl chlorides that inorganic acid is added carries out acyl chloride reaction.
It is further preferable that S1 Chinese styles（Ⅱ）The molar ratio of shown carboxylic acid perfluor polytrimethylene ether and acyl chlorides is 1:6~1:10.
It is further preferable that the solvent in S1 is perfluoropolyether HFE-7100；The solvent and formula（Ⅱ）Shown carboxylic acid perfluor
The Molar ratio of polytrimethylene ether is 5 ~ 25 mL/mmol.
It is further preferable that the acyl chlorides is one or more of thionyl chloride, phosphorus trichloride or oxalyl chloride.
It is further preferable that the temperature of the acyl chloride reaction is 30 ~ 100 DEG C, the time is 1 ~ 30h.
It is further preferable that in S1 after acyl chloride reaction, product is washed with chloroform, is layered, removes unreacted acyl chlorides.
The present invention provides a kind of preparation method converting terminal hydroxy group compound to Amino End Group compound.
Preferably, the process of sulfonylation is in S2：By formula（Ⅳ）Shown terminal hydroxy group compound adds after being mixed with TsCl solution
Enter after highly basic carries out sulfonylation and obtains intermediate product 1；The process of reduction is：By intermediate product 1 and potassium phthalimide
Salt is dissolved in flow back in DMF after, hydrazine hydrate and alcoholic solution is added, up to formula after stirring, dissolving, filtering, purification（Ⅴ）Shown end
Amino-compound；
。
Specific reaction process example is as follows：
Preferably, during sulfonylation, the highly basic is sodium hydroxide powder.Using grind broken sodium hydroxide powder as
Agent is fettered, reaction temperature can be more effectively controlled, shortens the time, improves yield.
Preferably, during reduction, the alcoholic solvent is absolute ethyl alcohol.
Preferably, S3 Chinese styles（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides and formula（Ⅴ）The molar ratio of shown Amino End Group compound is
1:1~1:3。
Preferably, amide reaction is in S3：By formula（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides is dissolved in solvent, and formula is added
（Ⅴ）Shown Amino End Group compound, return stirring is up to the surfactant.
It is further preferable that the solvent is the in the mixed solvent of perfluoropolyether HFE-7100 and trifluoromethy benzene BTF.
It is further preferable that the temperature of return stirring is 30-100 DEG C, the time is 8 ~ 36 h.
It is further preferable that revolving removes solvent after return stirring, extraction, drying are drained to constant weight and are lived up to surface
Property agent.
It is further preferable that the solvent of extraction is water or DMSO.
It is further preferable that being dried using drier；The drier is in anhydrous magnesium sulfate or anhydrous calcium chloride
It is one or more of.
It is more preferably, the surfactant drained is molten to further increase the purity of gained surfactant
Solution further purifies in methanol, this step may make the product of usual vehicle indissoluble to be precipitated, and what is taken after dry is exactly to be wanted
Fluorinated surfactant product, simplify reaction purification process, improve the purity and yield of product.
Above-mentioned surfactant is dissolved in carbon fluorocarbon oil and is used as surfactant product.The surfactant is in carbon
Mass fraction in fluorocarbon oil is 0.5 ~ 7%.
Application of the above-mentioned fluorine-containing nonionic surfactant in vitro in culture field is also within the scope of the present invention.
Compared with prior art, the present invention has the advantages that：
The fluorine-containing nonionic surfactant of amide bond provided by the invention is by carboxylic acid perfluor polytrimethylene ether and specific hydrophily
Amino-compound is obtained by the reaction by amide, has good bio-compatibility and stability, and purity is high, can be widely used for external
In the IVC of culture field.In addition, the product purity and yield that preparation method provided by the invention is prepared are high, it is simple for process.
Description of the drawings
The nuclear-magnetism fluorine spectrum that Fig. 1 is the PFPE-PEP105-PFEP that embodiment 1 provides；
Fig. 2 is the infrared spectrum for the PFPE-PEP105-PFPE that embodiment 1 provides；
Fig. 3 is drop microscope figures of the PFPE-PEP105-PFPE that provides of embodiment 1 in different phase, the outlet of (a) chip
Place；(b) after drop stands 7 days；(c) after drop carries out 34 PCR thermal cycles；
Fig. 4 is the PFPE-PEP105-PFPE bio-compatibilities test that embodiment 1 provides：(a) real time PCR curves, (b) Ct values
Comparison.
Specific implementation mode
With reference to embodiment, the present invention is further explained.These embodiments are merely to illustrate the present invention rather than limitation
The scope of the present invention.Test method without specific conditions in lower example embodiment usually according to this field normal condition or is pressed
The condition suggested according to manufacturer；Used raw material, reagent etc., unless otherwise specified, being can be from the business such as conventional market
The raw materials and reagents that approach obtains.The variation for any unsubstantiality that those skilled in the art is done on the basis of the present invention
And it replaces and belongs to scope of the present invention.
1 fluorinated surfactant PFPE-PEP105-PFPE of embodiment
Surfactant provided in this embodiment such as formula（Ⅰ）It is shown：
Wherein, 45 m, x+z 60, y 42, x 30, z 30.It is prepared by following steps：
（1）Starting carboxylic acid's perfluor polytrimethylene ether（M ~ 7500 g/mol）It is dissolved in solvent, under nitrogen protection, slowly adds thereto
The thionyl chloride for entering 6 equivalents carries out chloride under being acted at 55 DEG C, obtains perfluor polytrimethylene ether acyl chlorides；After reaction, chlorine is used
It is imitative to wash product, it is layered, removes unreacted chloride reagent.Remaining product 1 after chloride reagent will finally be removed（Such as formula
（Ⅲ））It is transferred in reaction vessel in case reacting in next step.
（2）The acquisition of hydrophilic ammonia based compound：Under nitrogen protection, 9.0 g compound both-end hydroxy compounds are molten
In methylene chloride, ice-water bath is cooled to 0 DEG C to solution.Then in methylene chloride by 4.0 g TsCl dissolvings, and it is slowly added
Enter in reaction vessel, after 4.0 g ground into broken NaOH be added reaction in batches, after 0 DEG C of 3 h of reaction, with dichloromethane and
Water extraction reaction three times, is collected organic phase and is dried with anhydrous magnesium sulfate, rotate, be dried under vacuum to constant weight and obtain intermediate product 1, produce
Rate is 98%.Under nitrogen protection, 6.0 g products 2 and 3.7 g potassium phthalimides are dissolved in 120 mL DMF,
12 h of reaction, revolving are stirred at reflux at 120 DEG C.2.5 mL hydrazine hydrates and 120 mL absolute ethyl alcohols are added, 80 DEG C of stirrings are anti-
It after answering 12 h, then is dissolved with a certain amount of dichloromethane, is collected by filtration filtered fluid, revolving is purified after removing solvent with silicagel column, is obtained
To product 2（Such as formula（Ⅴ）It is shown）, yield 45%.
（3）Step（1）In product 1 and step 2 in product 2 carry out the perfluor nonionic table that amide bond is obtained by the reaction
Face activating agent.A certain amount of product 1 is dissolved in perfluoropolyether HFE-7100 and trifluoromethy benzene（BTF）Mixed solvent
In, the product 2 of 2 equivalents is added thereto, reacts 12 h in 60 DEG C of return stirrings, revolving removal solvent uses HFE-7100/
The mixed solvent of DMSO is extracted three times, and organic phase, the solvent in revolving removal organic phase are collected, and vacuum is drained to constant weight,
Target product surface activating agent is obtained, the yield of whole process is 48%.
2 fluorinated surfactant PFPE-PEP105-PFPE of embodiment
Surfactant provided in this embodiment such as formula（Ⅰ）It is shown：
Wherein, it be 8 ~ 130, y is 12 ~ 75 that m, which is 25 ~ 80, x+z, the molecular weight of the surfactant of gained is 16000 ~
23000.It is prepared by following steps：
（1）Starting carboxylic acid's perfluor polytrimethylene ether（M ~ 7500 g/mol）It is dissolved in solvent, under nitrogen protection, slowly adds thereto
The oxalyl chloride for entering 8 equivalents carries out chloride under being acted at 55 DEG C, obtains perfluor polytrimethylene ether acyl chlorides；After reaction, chloroform is used
Product is washed, is layered, removes unreacted chloride reagent.Remaining product 1 after chloride reagent will finally be removed（Such as formula
（Ⅲ））It is transferred in reaction vessel in case reacting in next step.
（2）The acquisition of hydrophilic ammonia based compound：Under nitrogen protection, 9.0 g compound both-end hydroxy compounds are molten
In methylene chloride, ice-water bath is cooled to 0 DEG C to solution.Then in methylene chloride by 4.0 g TsCl dissolvings, and it is slowly added
Enter in reaction vessel, after 4.0 g ground into broken NaOH be added reaction in batches, after 0 DEG C of 3 h of reaction, with dichloromethane and
Water extraction reaction three times, is collected organic phase and is dried with anhydrous magnesium sulfate, rotate, be dried under vacuum to constant weight and obtain intermediate product 1, produce
Rate is 98%.Under nitrogen protection, 6.0 g products 2 and 3.7 g potassium phthalimides are dissolved in 120 mL DMF,
12 h of reaction, revolving are stirred at reflux at 120 DEG C.2.5 mL hydrazine hydrates and 120 mL absolute ethyl alcohols are added, 80 DEG C of stirrings are anti-
It after answering 12 h, then is dissolved with a certain amount of dichloromethane, is collected by filtration filtered fluid, revolving is purified after removing solvent with silicagel column, is obtained
To product 2（Such as formula（Ⅴ）It is shown）, yield 42.5%.
（3）Step（1）In product 1 and step 2 in product 2 carry out the perfluor nonionic table that amide bond is obtained by the reaction
Face activating agent.A certain amount of product 1 is dissolved in perfluoropolyether HFE-7100 and trifluoromethy benzene（BTF）Mixed solvent
In, the product 2 of 2 equivalents is added thereto, reacts 12 h in 60 DEG C of return stirrings, revolving removal solvent uses HFE-7100/
The mixed solvent of DMSO is extracted three times, and organic phase, the solvent in revolving removal organic phase are collected, and vacuum is drained to constant weight,
Target product surface activating agent is obtained, the yield of whole process is 46.5%.
3 fluorinated surfactant PFPE-PEP105-PFPE of embodiment
Surfactant provided in this embodiment such as formula（Ⅰ）It is shown：
Wherein, m is 25 ~ 45；X+z is that 12 ~ 90, y is 15 ~ 60, and gained surfactant molecule amount is 17000 ~ 23000.By such as
Lower step is prepared：
（1）Starting carboxylic acid's perfluor polytrimethylene ether（M ~ 7500 g/mol）It is dissolved in solvent, under nitrogen protection, slowly adds thereto
The thionyl chloride for entering 6 equivalents carries out chloride under being acted at 55 DEG C, obtains perfluor polytrimethylene ether acyl chlorides；After reaction, chlorine is used
It is imitative to wash product, it is layered, removes unreacted chloride reagent.Remaining product 1 after chloride reagent will finally be removed（Such as formula
（Ⅲ））It is transferred in reaction vessel in case reacting in next step.
（2）The acquisition of hydrophilic ammonia based compound：Under nitrogen protection, 9.0 g compound both-end hydroxy compounds are molten
In methylene chloride, ice-water bath is cooled to 0 DEG C to solution.Then in methylene chloride by 4.0 g TsCl dissolvings, and it is slowly added
Enter in reaction vessel, after 4.0 g ground into broken NaOH be added reaction in batches, after 0 DEG C of 3 h of reaction, with dichloromethane and
Water extraction reaction three times, is collected organic phase and is dried with anhydrous magnesium sulfate, rotate, be dried under vacuum to constant weight and obtain intermediate product 1, produce
Rate is 98%.Under nitrogen protection, 6.0 g products 2 and 3.7 g potassium phthalimides are dissolved in 120 mL DMF,
12 h of reaction, revolving are stirred at reflux at 120 DEG C.2.5 mL hydrazine hydrates and 120 mL absolute ethyl alcohols are added, 80 DEG C of stirrings are anti-
It after answering 12 h, then is dissolved with a certain amount of dichloromethane, is collected by filtration filtered fluid, revolving is purified after removing solvent with silicagel column, is obtained
To product 2（Such as formula（Ⅴ）It is shown）, yield 45%.
（3）Step（1）In product 1 and step 2 in product 2 carry out the perfluor nonionic table that amide bond is obtained by the reaction
Face activating agent.A certain amount of product 1 is dissolved in perfluoropolyether HFE-7100 and trifluoromethy benzene（BTF）Mixed solvent
In, the product 2 of 2 equivalents is added thereto, reacts 3 h in 100 DEG C of return stirrings, revolving removal solvent uses HFE-7100/
The mixed solvent of DMSO is extracted three times, and organic phase, the solvent in revolving removal organic phase are collected, and vacuum is drained to constant weight,
Target product surface activating agent is obtained, the yield of whole process is 42%.
Performance test
（1）Fluorine is composed and IR Characterization
Nuclear-magnetism fluorine stave sign and FI-IR characterizations are carried out to the surfactant that embodiment 1 provides.Fig. 1 is the surfactant
Nuclear-magnetism fluorine compose characterize data, change from the figure, it can be seen that apparent chemical shift occurs in the fluorine atom that is connected with carbonyl；Fig. 2
For the infared spectrum data of the surfactant, 1690 cm are can see from data-1There is apparent product amide C=O in position
Characteristic absorption peak.In conjunction with Fig. 1 and Fig. 2 data verifications structure of PFPE-PEP105-PFPE.
（2）Heat stability testing
The surfactant PFPE-PEP105-PFPE that case study on implementation 1 is obtained for drop it is micro-fluidic in, and verify its heat
Stability, specific verification method are as follows：
PFPE-PEP105-PFPE is dissolved in HFE-7500, the solution that mass fraction is 0.2 ~ 10% is made into.It is used as outer
Phase, deionized water do interior phase, and drop is carried out in micro-fluidic chip and generates experiment.After drop generation, pass through temperature programming
To certain temperature, verification is micro-fluidic to obtain the thermal stability of drop.Temperature Programmed Processes are to be raised to 55 DEG C from room temperature, at 55 DEG C
After maintaining 30 s, after rise to 72 DEG C from 55 DEG C, and maintain 30 s, then be warming up to 95 DEG C, and 60 s are maintained at 95 DEG C, with
Upper whole process repeats 35 times.The standing stability and thermal stability of drop obtained by micro- sem observation is used in combination.Fig. 3 is different phase
Drop observation chart under the microscope.It can be seen from the figure that after microlayer model stands 7 days again, stability is fine.Using
After 34 PCR thermal cycles, the stability of most drops all keeps fine, and only small part drop is merged,
But the requirement of PCR thermal cycles can be met.
（3）Bio-compatibility is tested
The surfactant that case study on implementation 1 is provided is used for PCR amplification.First prepare water-oil phase material.Oil phase material be dissolved with
The HFE-7500 solution of 1.5% PFPE-PEP105-PFPE, water-phase material are the 0.2 μ L templates cDNA containing 4.4 μ L water, 5
Μ l mix, 0.2 μ L sense primers, the aqueous solution of 0.2 μ L downstream primers.Water-oil phase material is pressed 2:8 volume ratio is mixed
It closes, PCR amplification experiment will be carried out after mixing.The process of PCR cycle is：First 95 DEG C, 10 s mono- cycles；Then respectively 95
DEG C when, keep 5 s and 60 DEG C at maintain 30 s, this process does 40 cycles.Experimental result is as shown in Figure 4.From real-time
PCR curve can be seen that pure water and added 1.5% PFPE-PE P105-PFPE HFE-7500 solution blank group with following
The increase of ring number, fluorescence intensity all remain essentially as zero；HFE-7500 containing 1.5% PFPE-PEP105-PFPE is molten
Liquid has good bio-compatibility.
Claims (10)
1. a kind of fluorine-containing nonionic surfactant of amide bond, which is characterized in that the surfactant such as formula（Ⅰ）Institute
Show：
Wherein, it be 8 ~ 130, y is 12 ~ 75 that m, which is 25 ~ 80, x+z,.
2. fluorine-containing nonionic surfactant according to claim 1, which is characterized in that m is 25 ~ 45；X+z is 12 ~ 90, y
It is 15 ~ 60.
3. fluorine-containing nonionic surfactant according to claim 2, which is characterized in that m 45；X+z is 60, y 42.
4. fluorine-containing nonionic surfactant according to claim 1, which is characterized in that the average mark of the surfactant
Son amount is 16000 ~ 23000.
5. the preparation method of any fluorine-containing nonionic surfactant of claim 1 ~ 4, which is characterized in that including walking as follows
Suddenly：
S1：By formula（Ⅱ）Shown carboxylic acid perfluor polytrimethylene ether chloride, obtains formula（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides；
S2：By formula（Ⅳ）It is formula using hydrazine hydrate reduction after shown terminal hydroxy group compound sulfonylation（Ⅴ）Shown Amino End Group chemical combination
Object；
S3：Formula（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides and formula（Ⅴ）Shown Amino End Group compound carries out amide and reacts up to the table
Face activating agent.
6. preparation method according to claim 5, which is characterized in that the process of chloride is in S1：By formula（Ⅱ）Shown carboxylic
Sour perfluor polytrimethylene ether is dissolved in solvent, in N2Under atmosphere, the acyl chlorides that inorganic acid is added carries out acyl chloride reaction.
7. preparation method according to claim 5, which is characterized in that the process of sulfonylation is in S2：By formula（Ⅳ）Shown end
Hydroxy compounds is added after highly basic carries out sulfonylation after being mixed with TsCl solution and obtains intermediate product 1；The process of reduction is：It will
Intermediate product 1 and potassium phthalimide are dissolved in DMF after reflux, and hydrazine hydrate and alcohol is added, stir, dissolving, filter,
Up to formula after purification（Ⅴ）Shown Amino End Group compound；
。
8. preparation method according to claim 5, which is characterized in that S3 Chinese styles（Ⅲ）Shown perfluor polytrimethylene ether acyl chlorides and formula
（Ⅴ）The molar ratio of shown Amino End Group compound is 1:1~1:3.
9. preparation method according to claim 5, which is characterized in that amide, which reacts, in S3 is：By formula（Ⅲ）Shown perfluor is poly-
Ether acyl chlorides is dissolved in solvent, and formula is added（Ⅴ）Shown Amino End Group compound, return stirring is up to the surfactant.
10. the application in culture field in vitro of any fluorine-containing nonionic surfactant of claim 1 ~ 4.
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| CN201810089846.5A CN108285537A (en) | 2018-01-30 | 2018-01-30 | A kind of fluorine-containing nonionic surfactant of amide bond and its preparation method and application |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112495316A (en) * | 2020-10-20 | 2021-03-16 | 大连理工大学 | Method for preparing micro-nano gel microspheres based on metastable emulsion |
| CN114292393A (en) * | 2021-12-14 | 2022-04-08 | 上海大学 | Branched fluorine-containing surfactant, preparation method and application thereof |
| CN114539536A (en) * | 2022-02-18 | 2022-05-27 | 华南师范大学 | Preparation method and application of perfluoropolyether surfactant containing amide bonds |
| CN115368576A (en) * | 2022-08-22 | 2022-11-22 | 苏州中科医疗器械产业发展有限公司 | Perfluoropolyether-adipic dihydrazide block copolymer, and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105189785A (en) * | 2013-03-08 | 2015-12-23 | 伯乐生命医学产品有限公司 | Compositions, methods and systems for polymerase chain reaction assays |
| CN106823986A (en) * | 2017-01-20 | 2017-06-13 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Three-stage fluorine surfactant and its preparation method and application |
-
2018
- 2018-01-30 CN CN201810089846.5A patent/CN108285537A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105189785A (en) * | 2013-03-08 | 2015-12-23 | 伯乐生命医学产品有限公司 | Compositions, methods and systems for polymerase chain reaction assays |
| CN106823986A (en) * | 2017-01-20 | 2017-06-13 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Three-stage fluorine surfactant and its preparation method and application |
Non-Patent Citations (4)
| Title |
|---|
| FABIILLI, MARIO L: "Delivery of Water-Soluble Drugs Using Acoustically Triggered", 《PHARMACEUTICAL RESEARCH》 * |
| JAN-WILLI JANIESCH: "Key Factors for Stable Retention of Fluorophores and Labeled", 《ANALYTICAL CHEMISTRY》 * |
| QUENTIN BROSSEAU: "Microfluidic Dynamic Interfacial Tensiometry", 《SOFT MATTER》 * |
| WADIM L. MATOCHKO: "Uniform amplification of phage display libraries in monodisperse emulsions", 《METHODS》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112495316A (en) * | 2020-10-20 | 2021-03-16 | 大连理工大学 | Method for preparing micro-nano gel microspheres based on metastable emulsion |
| CN114292393A (en) * | 2021-12-14 | 2022-04-08 | 上海大学 | Branched fluorine-containing surfactant, preparation method and application thereof |
| CN114292393B (en) * | 2021-12-14 | 2024-05-14 | 上海大学 | Dendronized fluorine-containing surfactant, preparation method and application thereof |
| CN114539536A (en) * | 2022-02-18 | 2022-05-27 | 华南师范大学 | Preparation method and application of perfluoropolyether surfactant containing amide bonds |
| CN115368576A (en) * | 2022-08-22 | 2022-11-22 | 苏州中科医疗器械产业发展有限公司 | Perfluoropolyether-adipic dihydrazide block copolymer, and preparation method and application thereof |
| CN115368576B (en) * | 2022-08-22 | 2023-06-16 | 苏州中科医疗器械产业发展有限公司 | Perfluoropolyether-adipic acid dihydrazide block copolymer and preparation method and application thereof |
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