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CN106552603A - PH response type magnetic metal organic frame composite nano materials and preparation method and application - Google Patents

PH response type magnetic metal organic frame composite nano materials and preparation method and application Download PDF

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CN106552603A
CN106552603A CN201610994774.XA CN201610994774A CN106552603A CN 106552603 A CN106552603 A CN 106552603A CN 201610994774 A CN201610994774 A CN 201610994774A CN 106552603 A CN106552603 A CN 106552603A
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metal organic
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CN106552603B (en
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蓝芳
杨琦
吴尧
顾忠伟
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Sichuan University
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Abstract

The invention discloses a kind of pH response types magnetic metal organic frame composite nano materials and preparation method and application, the composite nano materials are by Fe3O4Nanoparticle, is coated on Fe3O4The macromolecule layer of nanoparticle surface and the metal organic frame being grown on macromolecule layer are constituted；Macromolecule layer is constituted for the first polymer or the first polymer by chelated metal ions and hydrophilic second polymer of chelated metal ions；Metal organic frame is by Fe3+With the phenyl boronic acid derivative containing at least one carboxyl or at least two boronates by being coordinated bond formed.The composite nano materials that the present invention is provided, with preferable magnetic responsiveness energy, it is possible to the capture of reversible, high selectivity and release glycoprotein under different pH environment, and pH environment is relatively mild, it is to avoid impact is produced on glycoprotein activity.

Description

PH response type magnetic metal organic frame composite nano materials and preparation method thereof with Using
Technical field
The invention belongs to magnetic composite nano Material Field, more particularly to pH response types magnetic metal organic frame are compound receive Rice material, its preparation method and the application in terms of glycoprotein capture and release.
Background technology
Protein glycosylation, i.e., be transferred to protein by sugar, under glycosyl transferase effect with the aminoacid shape on protein Into glycosidic bond, be a kind of form of the most common post translational modification of albumen, key player played in many biological actions, Such as cell adhesion, molecular recognition, signal transduction, protein folding and metabolic pathway etc..Abnormal glycosylation also with many diseases Sick relevant, such as diabetes, cancer, neurodegenerative diseases, cardiovascular disease etc..In order to more fully understand these biological mistakes Journey, or find new disease marker, it is necessary first to glycoprotein is captured and is discharged.
Within past 10 years, according to different mechanism, existing certain methods put forward the identification of specificity or separate sugared egg In vain/glycopeptide, such as agglutinin affinity chromatography is (referring to document Wu, J.；Zhu,J.；Yin,H.；Buckanovich,R.J.； Lubman,D.M.Analysis of glycan variation on glycoproteins from serum by the Reverse lectin-based ELISA assay.J.Proteome Res.2014,13,2197-2204), hydrazide chemistry method (referring to document Liu, L.；Yu,M.；Zhang,Y.；Wang,C.；Lu,H.Hydrazide functionalized core- shell magnetic nanocomposites for highly specific enrichment of N- Glycopeptides.ACS Appl.Mater.Interfaces 2014,6,823-7832), hydrophilic interaction chromatography (referring to document Zhu, J.；Sun,Z.；Cheng,K.；Chen,R.；Ye,M.；Xu,B.；Sun,D.；Wang,L.；Liu,J.； Wang,F.；Zou,H.Comprehensive mapping of protein N-glycosylation in human liver by combining hydrophilic interaction chromatography and hydrazide Chemistry.J.Proteome Res.2014,13,1713-1721) and boric acid affinity chromatography (participation document Li, D.； Chen,Y.；Liu,Z.Boronate affinity materials for separation and molecular recognition:structure,properties and applications.Chem.Soc.Rev.2015,44,8097- 8123).At present, cause extensive concern realizes that glycoprotein capture and detached method are by the parent of the boric acid with pH switch performances The strategy combined with the magnetic nano-particle with unique magnetic properties with chromatograph, usually in magnetic Nano material surface modification The boronic acid ligands of small molecule, first, magnetic Nano material by many more manipulations by pre- functionalization active group (as carboxyl, amino, Azido etc.), then these active groups are reacted with the active group (such as amino, alkynyl etc.) of small molecule boronic acid ligands again, from And small molecule boronic acid ligands are (referring to document hang, L. in grafting；Xu,Y.；Yao,H.；Xie,L.；Yao,J.；Lu,H.；Yang, P.Boronic acid functionalized core-satellite composite nanoparticles for advanced enrichment of glycopeptides and glycoproteins.Chem.Eur.J.2009,15, 10158-10166)；However, during its capture or release glycoprotein, required pH of cushioning fluid is highly acid or highly basic Property, it is unfavorable for keeping the activity of glycoprotein, and, the preparation process of the magnetic composite nano material of boric acid functionalization is more numerous It is trivial, preparation cost has been significantly greatly increased, small molecule boronic acid ligands grafting amount is because which is larger sterically hindered so that boric acid is transferred in addition Connect less efficient, so as to limit its application in biomedical aspect.Therefore, research and develop a kind of energy simple and effective in gentle pH Capture and discharge the strategy of glycoprotein under environment with high selectivity, be a very meaningful and urgent job.
Metal organic frame (Metal-Organic Frameworks, MOFs) is passed through by metal ion and organic ligand What coordinate bond or intermolecular force were formed., centered on metal ion, with higher porosity, excellent machinery is steady for MOFs Surface property that is qualitative and being easy to adjustment, and which has abundant aromatic ligand, unique property due to more than, metal have machine frame Frame is widely used in different fields, such as separation of energy storage, catalysis, small molecule receptor, benzene homologue etc..Recently, MOFs It is widely used in biomedical sector, such as drug release, photodynamic therapy, development, enzyme catalysiss and protein enrichment etc.. It is related in the application of albumen, scientists focus primarily upon the capture rate for improving protein, and have ignored the release of albumen Process, is difficult to elute from material by the protein that MOFs is captured, that is, allows to be eluted, as elution process is needed Add material influential on protein active, such as 2-methylimidazole or trifluoroacetic acid (referring to document W.L.Liu, S.H.Lo, B.Singco,C.C.Yang,H.Y.Huang and C.H.Lin,J.Mater.Chem.B,2013,1,928；M.Zhao, C.Deng and X.Zhang,Chem.Commun.,2014,50,6228；N.Sun,X.Zhang and C.Deng, Nanoscale,2015,7,6487；M.Zhao,X.Zhang and C.Deng,Chem.Commun.,2015,51,8116； Y.Chen,Z.Xiong,L.Peng,Y.Gan,Y.Zhao,J.Shen,J.Qian,L.Zhang and W.Zhang,ACS Appl.Mater.Interfaces,2015,7,16338；J.Zheng,Z.Lin,G.Lin,H.Yang and L.Zhang, J.Mater.Chem.B, 2015,5,2185.), the further analysis to the protein after release or application can be had a strong impact on.
The content of the invention
The purpose of the present invention aims to above-mentioned problems of the prior art, there is provided a kind of pH response types magnetic metal Organic frame composite nano materials, can under gentle pH environment reversible, high selectivity capture or release glycoprotein.
Another object of the present invention aims to provide that a kind of reaction condition is gentle, the preparation method that preparation cost is low, for preparing Above-mentioned pH response types magnetic metal organic frame composite nano materials.
Still a further object of the present invention aims to provide above-mentioned pH response types magnetic composite nano ball in glycoprotein is captured or discharged Application.
In order to achieve the above object, the present invention takes technical scheme below to realize.
The invention provides a kind of pH response types magnetic metal organic frame composite nano materials, the composite nano materials by Fe3O4Nanoparticle, is coated on Fe3O4The macromolecule layer of nanoparticle surface and the metal being grown on macromolecule layer are organic Framework is constituted；First polymer or first polymer by chelated metal ions of the macromolecule layer for chelated metal ions Constitute with hydrophilic second polymer, when macromolecule layer is by the first polymer and hydrophilic second of chelated metal ions When polymer is constituted, the first polymer is 1 with the mass ratio of second polymer：(0.3～1)；The metal organic frame It is by Fe3+With the phenyl boronic acid derivative containing at least one carboxyl or at least two boronates by being coordinated bond formed.
Above-mentioned pH response types magnetic metal organic frame composite nano materials, first polymer be polyvinylpyrrolidone or Poly-dopamine；The second polymer is Polyetherimide or polyacrylic acid；Phenyl boronic acid derivative containing at least one carboxyl For 5- boronate M-phthalic acids (5-Boronoisophthalic acid), 3- Carboxybenzeneboronic acids or 4- Carboxybenzeneboronic acids, institute It is to benzene hypoboric acid or isophthalic hypoboric acid to state the phenyl boronic acid derivative containing at least two boronates.
The average particle size distribution of above-mentioned pH response types magnetic metal organic frame composite nano materials is narrow, and about 300nm～ 500nm.The magnetic metal organic frame composite nano materials are by Fe3O4Nanoparticle as core, with high magnetic saturation intensity, So as to provide preferable magnetic responsiveness energy；It is wrapped in Fe3O4The macromolecule layer of nanoparticle surface is not only improved as transition zone The hydrophilic of material, and can chelated metal ions, the metal organic frame (MOFs) is grown on the macromolecule layer；Most The metal organic frame of outer layer is by Fe3+Pass through with the phenyl boronic acid derivative containing at least one carboxyl or at least two boronates Coordination bond formed, wherein the phenyl boronic acid derivative containing at least one carboxyl or at least two boronates is both organic as metal The organic ligand of framework, and as the functional molecular with pH responses and capture protein, so as to give material pH responses The ability of energy and selectivity capture protein.
Invention further provides the preparation method of above-mentioned pH response types magnetic metal organic frame composite nano materials, The ultimate principle of the preparation method is to prepare Fe first with solvent-thermal method3O4Nanoparticle；Again in obtained Fe3O4Nanoparticle Sub- Surface coating mixes macromolecule layer by first polymer and hydrophilic second polymer, and macromolecule layer cladding is obtained Fe3O4/ Polymer nanoparticles；Then using solubility trivalent iron salt as source metal, containing at least one carboxyl or at least MOFs is grown in Fe by one kettle way as organic ligand by the phenyl boronic acid derivative of two boronates3O4/ Polymer nanoparticles Sublist face obtains pH response type magnetic metal organic frame composite nano materials.
The preparation side of the pH response type magnetic metal organic frame composite nano materials provided based on above-mentioned principle, the present invention Method, step are as follows：
(1) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By Fe3O4Nanoparticle is distributed in deionized water, prepares Fe3O4Nanoparticle concentration is 40～80mg/mL's Fe3O4Nanoparticle suspension；First polymer or first polymer and second polymer are dissolved in deionized water, the is prepared One polymer concentration is 55～85mg/ml or first polymer and the macromolecule that second polymer total concentration is 55～85mg/ml Aqueous solution, when first polymer is dissolved in deionized water with second polymer, the quality of first polymer and second polymer Than for 1：(0.3～1)；
(2) prepare Fe3O4/ Polymer nanoparticles
The Fe that step (1) is prepared3O4Nanoparticle suspension and water-soluble polymers are according to volume ratio 1：(2～6) measure And be added in reaction vessel, the first reactant liquor is obtained within least 8 hours in room temperature reaction under agitation, then collect first with Magnet Solid product in reactant liquor, then deionized water, ethanol and DMF are obtained to solid product washing successively Fe3O4/ Polymer nanoparticles；
(3) pH response type magnetic metal organic frame composite nano materials are prepared
By the Fe after washing obtained by step (2)3O4/ Polymer nanoparticles are distributed in DMF, are obtained To the Fe that concentration is 65～95mg/ml3O4/ Polymer nanoparticle suspensions；By bodies such as acetonitrile and N,N-dimethylformamides Product mix homogeneously obtains the first mixed liquor；By Fe3O4/ Polymer nanoparticle suspensions and N in the first mixed liquor, N- dimethyl The volume ratio of Methanamide is that 1 ︰ (1～16) measures Fe3O4/ Polymer nanoparticle suspensions and the first mixed liquor, under agitation By Fe3O4/ Polymer nanoparticle suspensions are added in the first mixed liquor, and are stirred to Fe3O4/ Polymer nanoparticles It is uniformly dispersed and obtains the second mixed liquor；Under agitation, in the second mixed liquor add solubility trivalent iron salt and contain at least one The phenyl boronic acid derivative of individual carboxyl or at least two boronates is simultaneously uniformly mixing to obtain the 3rd mixed liquor, and the phenylboric acid derives The addition of thing on the basis of the content of DMF in the second mixed liquor, per 6～10ml N, N- dimethyl formyls Amine adds 1 mM of phenyl boronic acid derivative, and the solubility trivalent iron salt is (0.5～2) with the mol ratio of phenyl boronic acid derivative: 1；The 3rd mixed liquor is warming up to into 100～130 DEG C of reactions under agitation and obtains the second reactant liquor within least 1 hour, use Magnet afterwards The solid product in the second reactant liquor is collected, then successively with DMF, ethanol and deionized water to solid product Washing obtains pH response type magnetic metal organic frame composite nano materials.
The preparation method of above-mentioned pH response types magnetic metal organic frame composite nano materials, Fe3O4Nanoparticle can be joined The customary preparation methods disclosed in examining prior art are obtained, referring to Zhao, M.；Zhang,X.；Deng,C.Rational synthesis of novel recyclable Fe3O4@MOF nanocomposites for enzymatic Digestion.Chem.Commun.2015,51,8116-8119 and Zhang, Y.；Yang,Y.；Ma,W.；Guo,J.；Lin, Y.；Wang,C.Uniform Magnetic Core/Shell Microspheres Functionalized with Ni2+- Iminodiacetic Acid for One Step Purification and Immobilization of His-Tagged Enzymes.ACS Appl.Mater.Interfaces 2013,5,2626-2633.The preparation method adopted in the present invention for： By raw material iron chloride, sodium citrate and ammonium acetate, in molar ratio 1：(0.33～0.79)：10 are added to and fill chlorination weight of iron In the reaction vessel of (33～36) solvent ethylene glycol again, material dissolution mix homogeneously are made under agitation；Then will reaction temperature Degree rises to 180～220 DEG C, and reaction was no less than 15 hours；Reaction temperature is cooled to room temperature after terminating by reaction again, is collected with Magnet Fe in reactant liquor3O4Nanoparticle；Then ethanol and deionized water are used successively to Fe3O4Nanoparticle carries out washing and removes not The raw material of reaction.
The preparation method of above-mentioned pH response types magnetic metal organic frame composite nano materials, the purpose of step (2) is profit With the first polymer of the first polymer or chelated metal ions of chelated metal ions together with hydrophilic second polymer By Fe3O4Nanoparticle cladding is complete, obtains the Fe of macromolecule layer parcel3O4Nanoparticle (i.e. Fe3O4/ Polymer nanoparticles Son), so as in Fe3O4Nanoparticle surface energy further growth MOFs, wherein, first polymer chelates MOFs as transition zone The metal ion of layer, makes MOFs layers in Fe3O4/ Polymer nanoparticle surface grows, and second polymer is used to increase material Hydrophilic, second polymer in this material it is not necessary to, but in order to improve dispersibility of the final material in water, enter And improve to protein capture and release efficiency, first polymer is preferably when macromolecule layer is constituted together with second polymer Select, now first polymer is preferably 1 with the mass ratio of second polymer：(0.3～1), preferably 1：(0.3～0.5).When Fe3O4Nanoparticle suspension and water-soluble polymers volume ratio are 1：When (2～6), Fe is can ensure that substantially3O4Nanoparticle It is complete by macromolecule layer cladding.After step (2) collects the solid product in the first reactant liquor with Magnet, need further to spend Ionized water, ethanol and N,N-dimethylformamide solid product washing is removed absorption solid product surface, unreacted the One polymer or second polymer, general every kind of wash liquid three to five times.
The preparation method of above-mentioned pH response types magnetic metal organic frame composite nano materials, the purpose of step (3) be The Fe that step (2) is obtained3O4/ Polymer nanoparticle surface grows MOFs layers, obtains pH response type magnetic metal organic frames Composite nano materials (i.e. Fe3O4/ Polymer/MOFs composite nano materials).Solubility trivalent iron salt is used to provide Fe3+, which can Think Fe (NO)3Or FeCl3, when solubility trivalent iron salt and the benzene boron containing at least one carboxyl or at least two boronates Acid derivative mol ratio is (0.5～2):1, particularly (0.8～1):When 1, the MOFs layers of formation show good pH responses Performance and protein adsorption selectivity.In order to improve Fe3O4/ Polymer nanoparticle surface chelated metal ions are imitated Rate, Fe3O4The adding proportion of/Polymer nanoparticle suspensions and mixed liquor should be according to middle Fe3O4/ Polymer nanoparticles Suspension and N,N-dimethylformamide volume ratio 1：(1～16) add, which is preferably in a proportion of 1：(6～10), work as Fe3O4/ Polymer nanoparticle additions are very few, are unfavorable for Fe3O4/ Polymer nanoparticle surface forms MOFs layers, and works as Fe3O4/ When Polymer nanoparticle additions are excessive, Fe is easily caused3O4The aggregation of/Polymer nanoparticles, is equally unfavorable for Fe3O4/ Polymer nanoparticle surface forms MOFs layers.Step (3) with Magnet collect the second reactant liquor in solid product it Afterwards, need further solid product to be washed with DMF, ethanol and deionized water removing absorption in solid product The mixed liquor on thing surface and unreacted phenyl boronic acid derivative etc., general every kind of wash liquid three to five times.
The preparation method of above-mentioned pH response types magnetic metal organic frame composite nano materials, the first polymer is poly- Vinylpyrrolidone or poly-dopamine；The second polymer is Polyetherimide or polyacrylic acid；The solubility ferric iron Salt is Fe (NO)3Or FeCl3；The phenyl boronic acid derivative containing at least one carboxyl is 5- boronate M-phthalic acids, 3- carboxylics Base phenylboric acid or 4- Carboxybenzeneboronic acids, the phenyl boronic acid derivative containing at least two boronates are to benzene hypoboric acid or isophthalic Hypoboric acid.
Invention further provides a kind of above-mentioned pH response types magnetic metal organic frame composite nano materials are in sugared egg Application in white capture or glycoprotein release；It is the magnetic metal organic frame composite nano materials under neutral environment in pH The phenylboric acid on surface can covalently form cyclic ethers with the c/s-diol of glycoprotein, and realize the capture to glycoprotein；And work as environment pH When being converted to 8～9 alkaline environment, it becomes possible to reversible release glycoprotein, i.e., described magnetic metal organic frame composite Nano The glycoprotein for capturing is discharged by material.
The capture of above-mentioned glycoprotein and method for releasing, can be used for capturing and discharging the glycoprotein of any type, example Such as transferrinss, horseradish peroxidase, alpha-fetoprotein etc..
Compared with prior art, the invention has the advantages that：
1st, the pH response type magnetic metal organic frame composite nano materials that the present invention is provided, with Fe3O4Nanoparticle conduct Core, with high magnetic saturation intensity, so as to provide preferable magnetic responsiveness energy, can be completed in a relatively short time Magneto separate； Additionally, the MOFs layers on the composite nano materials surface include phenyl boronic acid derivative, and while as organic ligand, can be not With capture and the release glycoprotein of reversible, high selectivity under pH environment.
2nd, the pH response type magnetic metal organic frame composite nano materials that the present invention is provided, can realize that in pH be neutrality Glycoprotein, and under alkaline environment that pH be 8～9 reversible release glycoprotein, capture and release sugar are captured under environment effectively The pH environment of albumen is relatively mild, it is to avoid produce impact to glycoprotein activity.
3rd, the preparation method of the pH response type magnetic metal organic frame composite nano materials that the present invention is provided, operation letter Single, reaction condition is gentle, intermediate product Fe3O4/ Polymer nanoparticles are just obtained at ambient temperature, and Fe3O4/ Polymer nanoparticles, solubility trivalent iron salt and the phenylboric acid containing at least one carboxyl or at least two boronates spread out Biology can just prepare the composite nano materials at short notice using one kettle way, be thus susceptible to lead in biological medicine industry Promote in domain.
Description of the drawings
Fig. 1 is embodiment of the present invention Fe3O4The preparation flow figure of/Polymer/MOFs composite nano materials.
Fig. 2 uses Fe for the embodiment of the present invention3O4/ Polymer/MOFs composite nano materials are to sugar in albumen mixed system The capture of albumen and separation process figure.
Fig. 3 is embodiment of the present invention Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/Polymer/MOFs The structural characterization schematic diagram of composite nano materials, wherein (A), (D) and (G) is Fe3O4Scanning electron microscope (SEM) figure of nanoparticle, Transmission electron microscope (TEM) figure and size distribution plot (DLS), (B), (E) and (H) be Fe3O4The scanning electron microscope of/Polymer nanoparticles (SEM) figure, transmission electron microscope (TEM) figure and size distribution plot (DLS), (C), (F) and (I) be Fe3O4/ Polymer/MOFs is combined Scanning electron microscope (SEM) figure of nano material, transmission electron microscope (TEM) figure and size distribution plot (DLS).
Fig. 4 is embodiment of the present invention Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/Polymer/MOFs The Zeta potential figure of composite nano materials.
Fig. 5 is Fe3O4Nanoparticle (A), Fe3O4/ Polymer nanoparticles (B), Fe3O4/ Polymer/MOFs is compound to be received Energy Dispersive X-ray (EDX) energy spectrum diagram of rice material (C).
Fig. 6 is embodiment of the present invention PVP (a), PEI (b), PBA (c), Fe3O4Nanoparticle (d), Fe3O4/ Polymer receives Rice corpuscles (e), Fe3O4/ Polymer/MOFs composite nano materials (f) is in 4000～500 (cm of wave number-1) between infrared figure Spectrum.
Fig. 7 is embodiment of the present invention Fe3O4The attached isothermal of absorption-desorption of the nitrogen of/Polymer/MOFs composite nano materials Curve (A) and estimated using Barrett-Joyner-Halenda (BJH) according to nitrogen adsorption-desorption isothermal curve Fe3O4The aperture size distribution curve of/Polymer/MOFs composite nano materials.
Fig. 8 is embodiment of the present invention PVP (a), PBA (b), Fe3O4Nanoparticle (c), Fe3O4/ Polymer nanoparticles (d)、Fe3O4X-ray optical diffraction (XRD) collection of illustrative plates of/Polymer/MOFs composite nano materials (e), MOFs (f)；Wherein bottom Mark is Fe3O4Standard x RD diffraction maximum (JCPDS 19-06290).
Fig. 9 is embodiment of the present invention PVP (a), PBA (b), Fe3O4Nanoparticle (c), Fe3O4/ Polymer nanoparticles (d)、Fe3O4Thermogravimetric analysiss (TGA) figure of/Polymer/MOFs composite nano materials (e).
Figure 10 is embodiment of the present invention Fe3O4Nanoparticle (a), Fe3O4/ Polymer nanoparticles (b), Fe3O4/ Expanded view of the hysteresis curve figure (A) and gained hysteresis curve of Polymer/MOFs composite nano materials (d) in low field region (B)。
Figure 11 is embodiment of the present invention Fe3O4/ Polymer/MOFs composite nano materials are to non-magnet state and have Magnet The state diagram of response.
Figure 12 is embodiment of the present invention molecular weight standards (marker), mixed liquid of protein (Mix) and Fe3O4/Polymer/ MOFs composite nano materials be incubated under pH=7 environment before and after the standard specimen (Mix) of mixed liquid of protein, the supernatant (S), bonding The SDS- of the material (C) after the material (C) of albumen, and the eluent (E) after eluting under pH=7 or pH=9 environment, eluting PAGE analysis charts；Wherein, incubation process represents that with I elution process is represented with E.
Figure 13 is that molecular weight standards (marker), albumen biased sample (Mix) and commercial magnetic bead are incubated under pH=7 environment The standard specimen (Mix) of mixed liquid of protein in front and back, the supernatant (S), the material (C) of bonding albumen, and in pH=7 or pH=9 The SDS-PAGE analysis charts of the material (C) after eluent (E), eluting under environment after eluting；Wherein, incubation process represented with I, Elution process is represented with E.
Specific embodiment
Clear, complete description is carried out to the technical scheme of various embodiments of the present invention below with reference to accompanying drawing, it is clear that retouched State a part of embodiment that embodiment is only the present invention, rather than the embodiment of whole.Based on the embodiment in the present invention, this The resulting all other embodiment on the premise of creative work is not made of field those of ordinary skill, belongs to this Bright protected scope.
Embodiment 1 prepares Fe3O4/ Polymer/MOFs composite nano materials
In the present embodiment, macromolecule layer is polyvinylpyrrolidone (PVP), and metal organic frame is with ferric nitrate as metal Source, using Isosorbide-5-Nitrae-to benzene hypoboric acid (PBA) as organic ligand.
Fig. 1 gives Fe3O4The preparation flow figure of/Polymer/MOFs composite nano materials, first with solvent thermal legal system Standby surface shows electronegative Fe3O4Nanoparticle；Interact according to electrostatic interaction, Van der Waals force etc. again, in obtained Fe3O4 Nanoparticle surface coats a floor height molecular layer, obtains the Fe of macromolecule layer cladding3O4Nanosphere (Fe3O4/ Polymer nanoparticles Son)；Then using ferric nitrate be source metal, Isosorbide-5-Nitrae-to benzene hypoboric acid (PBA) as organic ligand, with Fe3O4/ Polymer nanoparticles Son prepares Fe by one kettle way together3O4/ Polymer/MOFs composite nano materials.
With reference to above-mentioned flow process, the present embodiment Fe3O4The preparation process of/Polymer/MOFs composite nano materials is as follows：
(1) prepare Fe3O4Nanoparticle
Raw material 1.157g ferric chloride hexahydrates, 1.0g sodium citrates and 3.303g ammonium acetates are added to and fill 57mL solvents In the politef stainless steel cauldron of ethylene glycol, magnetic agitation dissolves above-mentioned raw materials in 1 hour；Then stirrer is removed, Temperature of reaction kettle is risen to into 180 DEG C, is reacted 15 hours；Reactor is cooled to into room temperature again, with Magnet collect reaction obtain it is anti- Answer product in liquid；Then successively with ethanol to product repeated washing five times (10mL × 5), deionized water to product repeated washing Five times (10mL × 5) obtain Fe3O4Nanoparticle；
(2) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By the Fe after washing obtained by step (1)3O4Nanoparticle is distributed in 18.75ml deionized waters, prepares Fe3O4Receive Fe of the rice corpuscles concentration for 40mg/mL3O4Nanoparticle suspension；Polyvinylpyrrolidone (PVP) is dissolved in deionized water, Prepare water-soluble polymers of the PVP concentration for 55mg/ml；
(3) prepare Fe3O4/ Polymer nanoparticles
Take the 6.25mlFe that step (2) is prepared3O4Nanoparticle suspension and 12.5ml water-soluble polymers are added to reaction In container, the first reactant liquor is obtained within 8 hours in room temperature reaction under agitation, the solid then collected with Magnet in the first reactant liquor is produced Thing, then successively deionized water to product repeated washing five times (10mL × 5), with ethanol to five (10mL of product repeated washing × wash 5) and to product five times (10mL × 5) with N,N-dimethylformamide and obtain Fe3O4/ Polymer nanoparticles；
(4) prepare Fe3O4/Polymer/MOFs
By the Fe after washing obtained by step (3)3O4/ Polymer nanoparticles are distributed to 2.45ml N, N- dimethyl formyls In amine, the Fe that concentration is 65.3mg/ml is obtained3O4/ Polymer nanoparticle suspensions；By 6ml acetonitriles and 6ml N, N- diformazan Base Methanamide is mixed to get the first mixed liquor；Under agitation by 1ml Fe3O4/ Polymer nanoparticle suspensions are added to first In mixed liquor, and stir to Fe3O4/ Polymer nanoparticles are uniformly dispersed and obtain the second mixed liquor；Under agitation, it is mixed to second 202mgFe (NO are added in closing liquid3)3·9H2O and 160mg PBA are simultaneously uniformly mixing to obtain the 3rd mixed liquor；Under agitation by Three mixed liquors are warming up to 100 DEG C, and reaction obtains the second reactant liquor in 1 hour, collect the solid in the second reactant liquor with Magnet afterwards Product, then successively with DMF to product repeated washing five times (10mL × 5), with ethanol to product repeated washing Five times (10mL × 5) and deionized water obtain Fe to product repeated washing five times (10mL × 5)3O4/ Polymer/MOFs is combined Nano material.
Embodiment 2 prepares Fe3O4/ Polymer/MOFs composite nano materials
In the present embodiment, macromolecule layer is polyvinylpyrrolidone (PVP) and Polyetherimide (PEI), and metal has machine frame Frame with ferric nitrate as source metal, using Isosorbide-5-Nitrae-to benzene hypoboric acid (PBA) as organic ligand.
The present embodiment Fe3O4The preparation process of/Polymer/MOFs composite nano materials is as follows：
(1) prepare Fe3O4Nanoparticle
Raw material 1.157g ferric chloride hexahydrates, 0.4g sodium citrates and 3.303g ammonium acetates are added to and fill 60mL solvents In the politef stainless steel cauldron of ethylene glycol, magnetic agitation dissolves above-mentioned raw materials in 1 hour；Then stirrer is removed, Temperature of reaction kettle is risen to into 200 DEG C, is reacted 16 hours；Reactor is cooled to into room temperature again, with Magnet collect reaction obtain it is anti- Answer product in liquid；Then successively with ethanol to product repeated washing three times (15mL × 3), deionized water to product repeated washing Three times (15mL × 3) obtain Fe3O4Nanoparticle；
(2) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By the Fe after washing obtained by step (1)3O4Nanoparticle is distributed in 15ml deionized waters, prepares Fe3O4Nanoparticle Fe of the sub- concentration for 50mg/mL3O4Nanoparticle suspension；Polyvinylpyrrolidone (PVP) and Polyetherimide (PEI) are pressed According to mass ratio 1：0.4 is dissolved in deionized water, prepares water-soluble polymers of the PVP and PEI total concentrations for 70mg/ml；
(3) prepare Fe3O4/ Polymer nanoparticles
Take the 5mlFe that step (2) is prepared3O4Nanoparticle suspension and 20ml water-soluble polymers are added to reaction vessel In, the first reactant liquor is obtained within 12 hours in room temperature reaction under agitation, then collect the solid product in the first reactant liquor with Magnet, Again successively deionized water to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three times (15mL × 3) Fe is obtained with three times (15mL × 3) are washed with N,N-dimethylformamide to product3O4/ Polymer nanoparticles；
(4) prepare Fe3O4/ Polymer/MOFs composite nano materials
By the Fe after washing obtained by step (3)3O4/ Polymer nanoparticles are distributed to 2ml N,N-dimethylformamides In, obtain the Fe that concentration is 80mg/ml3O4/ Polymer nanoparticle suspensions；By 8ml acetonitriles and 8ml N, N- dimethyl methyl Amide is mixed to get the first mixed liquor；Under agitation by 1ml Fe3O4/ Polymer nanoparticle suspensions are added to the first mixing In liquid, and stir to Fe3O4/ Polymer nanoparticles are uniformly dispersed and obtain the second mixed liquor；Under agitation, to the second mixed liquor Middle addition 320mgFe (NO3)3·9H2O and 160mg PBA are simultaneously uniformly mixing to obtain the 3rd mixed liquor；Under agitation the 3rd is mixed Close liquid and be warming up to 120 DEG C, reaction obtains the second reactant liquor in 2 hours, the solid product in the second reactant liquor is collected with Magnet afterwards, Again successively with N,N-dimethylformamide to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three times (15mL × 3) and deionized water obtain Fe to product repeated washing three times (15mL × 3)3O4/ Polymer/MOFs composite Nanos Material.
Embodiment 3 prepares Fe3O4/ Polymer/MOFs composite nano materials
In the present embodiment, macromolecule layer is poly-dopamine (PDA) and polyacrylic acid (PAA), and metal organic frame is with chlorination Ferrum is source metal, using 3- Carboxybenzeneboronic acids as organic ligand.
The preparation process of the present embodiment Fe3O4/Polymer/MOFs composite nano materials is as follows：
(1) prepare Fe3O4Nanoparticle
Raw material 1.157g ferric chloride hexahydrates, 0.7g sodium citrates and 3.303g ammonium acetates are added to and fill 60mL solvents In the politef stainless steel cauldron of ethylene glycol, magnetic agitation dissolves above-mentioned raw materials in 1 hour；Then stirrer is removed, Temperature of reaction kettle is risen to into 220 DEG C, is reacted 17 hours；Reactor is cooled to into room temperature again, with Magnet collect reaction obtain it is anti- Answer product in liquid；Then successively with ethanol to product repeated washing three times (20mL × 3), deionized water to product repeated washing Three times (20mL × 3) obtain Fe3O4Nanoparticle；
(2) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By the Fe after washing obtained by step (1)3O4Nanoparticle is distributed in 9.4ml deionized waters, prepares Fe3O4Nanometer Fe of the particle concentration for 80mg/mL3O4Nanoparticle suspension；By poly-dopamine (PDA) and polyacrylic acid according to mass ratio 1：1 It is dissolved in deionized water, prepares water-soluble polymers of the PVP and PEI total concentrations for 85mg/ml；
(3) prepare Fe3O4/ Polymer nanoparticles
Take the 3.5mlFe that step (2) is prepared3O4Nanoparticle suspension and 21ml water-soluble polymers are added to reaction to be held In device, the first reactant liquor is obtained within 24 hours in room temperature reaction under agitation, the solid then collected with Magnet in the first reactant liquor is produced Thing, then successively deionized water to product repeated washing three times (15mL × 3), with ethanol to three (15mL of product repeated washing × wash 3) and to product three times (15mL × 3) with N,N-dimethylformamide and obtain Fe3O4/ Polymer nanoparticles；
(4) prepare Fe3O4/ Polymer/MOFs composite nano materials
By the Fe after washing obtained by step (3)3O4/ Polymer nanoparticles are distributed to 2ml N,N-dimethylformamides In, obtain the Fe that concentration is 95mg/ml3O4/ Polymer nanoparticle suspensions；By 16ml acetonitriles and 16ml N, N- dimethyl Methanamide is mixed to get the first mixed liquor；Under agitation by 1ml Fe3O4/ Polymer nanoparticle suspensions are added to first and mix Close in liquid, and stir to Fe3O4/ Polymer nanoparticles are uniformly dispersed and obtain the second mixed liquor；Under agitation, to the second mixing 650mgFeCl is added in liquid3With 332mg 3- Carboxybenzeneboronic acids and it is uniformly mixing to obtain the 3rd mixed liquor；Under agitation by the 3rd Mixed liquor is warming up to 130 DEG C, and reaction obtains the second reactant liquor in 8 hours, and the solid collected with Magnet in the second reactant liquor afterwards is produced Thing, then successively with DMF to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three Secondary (15mL × 3) and deionized water obtain Fe to product repeated washing three times (15mL × 3)3O4/ Polymer/MOFs is compound to be received Rice material.
Embodiment 4 prepares Fe3O4/ Polymer/MOFs composite nano materials
In the present embodiment, macromolecule layer is polyvinylpyrrolidone (PVP) and Polyetherimide (PEI), and metal has machine frame Frame with ferric nitrate as source metal, using 4- Carboxybenzeneboronic acids as organic ligand.
The present embodiment Fe3O4The preparation process of/Polymer/MOFs composite nano materials is as follows：
(1) prepare Fe3O4Nanoparticle
Raw material 1.157g ferric chloride hexahydrates, 0.4g sodium citrates and 3.303g ammonium acetates are added to and fill 60mL solvents In the politef stainless steel cauldron of ethylene glycol, magnetic agitation dissolves above-mentioned raw materials in 1 hour；Then stirrer is removed, Temperature of reaction kettle is risen to into 200 DEG C, is reacted 16 hours；Reactor is cooled to into room temperature again, with Magnet collect reaction obtain it is anti- Answer product in liquid；Then successively with ethanol to product repeated washing three times (15mL × 3), deionized water to product repeated washing Three times (15mL × 3) obtain Fe3O4Nanoparticle；
(2) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By the Fe after washing obtained by step (1)3O4Nanoparticle is distributed in 15ml deionized waters, prepares Fe3O4Nanoparticle Fe of the sub- concentration for 50mg/mL3O4Nanoparticle suspension；Polyvinylpyrrolidone (PVP) and Polyetherimide (PEI) are pressed According to mass ratio 1：0.3 is dissolved in deionized water, prepares water-soluble polymers of the PVP and PEI total concentrations for 70mg/ml；
(3) prepare Fe3O4/ Polymer nanoparticles
Take the 5mlFe that step (2) is prepared3O4Nanoparticle suspension and 15ml water-soluble polymers are added to reaction vessel In, the first reactant liquor is obtained within 10 hours in room temperature reaction under agitation, then collect the solid product in the first reactant liquor with Magnet, Again successively deionized water to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three times (15mL × 3) Fe is obtained with three times (15mL × 3) are washed with N,N-dimethylformamide to product3O4/ Polymer nanoparticles；
(4) prepare Fe3O4/ Polymer/MOFs composite nano materials
By the Fe after washing obtained by step (3)3O4/ Polymer nanoparticles are distributed to 2ml N,N-dimethylformamides In, obtain the Fe that concentration is 80mg/ml3O4/ Polymer nanoparticle suspensions；By 10ml acetonitriles and 10ml N, N- dimethyl Methanamide is mixed to get the first mixed liquor；Under agitation by 1ml Fe3O4/ Polymer nanoparticle suspensions are added to first and mix Close in liquid, and stir to Fe3O4/ Polymer nanoparticles are uniformly dispersed and obtain the second mixed liquor；Under agitation, to the second mixing 404mg Fe (NO are added in liquid3)3·9H2O and 166mg 4- Carboxybenzeneboronic acids are simultaneously uniformly mixing to obtain the 3rd mixed liquor；Stirring Mix it is lower 3rd mixed liquor is warming up to into 120 DEG C, reaction obtain the second reactant liquor within 4 hours, afterwards with Magnet collect the second reactant liquor In solid product, then successively with DMF to product repeated washing three times (15mL × 3), with ethanol to product Repeated washing three times (15mL × 3) and deionized water obtain Fe to product repeated washing three times (15mL × 3)3O4/Polymer/ MOFs composite nano materials.
Embodiment 5 prepares Fe3O4/ Polymer/MOFs composite nano materials
In the present embodiment, macromolecule layer is polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA), metal organic frame With iron chloride as source metal, using isophthalic hypoboric acid as organic ligand.
The present embodiment Fe3O4The preparation process of/Polymer/MOFs composite nano materials is as follows：
(1) prepare Fe3O4Nanoparticle
Raw material 1.157g ferric chloride hexahydrates, 0.4g sodium citrates and 3.303g ammonium acetates are added to and fill 60mL solvents In the politef stainless steel cauldron of ethylene glycol, magnetic agitation dissolves above-mentioned raw materials in 1 hour；Then stirrer is removed, Temperature of reaction kettle is risen to into 200 DEG C, is reacted 16 hours；Reactor is cooled to into room temperature again, with Magnet collect reaction obtain it is anti- Answer product in liquid；Then successively with ethanol to product repeated washing three times (15mL × 3), deionized water to product repeated washing Three times (15mL × 3) obtain Fe3O4Nanoparticle；
(2) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By the Fe after washing obtained by step (1)3O4Nanoparticle is distributed in 15ml deionized waters, prepares Fe3O4Nanoparticle Fe of the sub- concentration for 50mg/mL3O4Nanoparticle suspension；By polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) according to Mass ratio 1：0.5 is dissolved in deionized water, prepares water-soluble polymers of the PVP and PAA total concentrations for 70mg/ml；
(3) prepare Fe3O4/ Polymer nanoparticles
Take the 5mlFe that step (2) is prepared3O4Nanoparticle suspension and 25ml water-soluble polymers are added to reaction vessel In, the first reactant liquor is obtained within 14 hours in room temperature reaction under agitation, then collect the solid product in the first reactant liquor with Magnet, Again successively deionized water to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three times (15mL × 3) Fe is obtained with three times (15mL × 3) are washed with N,N-dimethylformamide to product3O4/ Polymer nanoparticles；
(4) prepare Fe3O4/ Polymer/MOFs composite nano materials
By the Fe after washing obtained by step (3)3O4/ Polymer nanoparticles are distributed to 2ml N,N-dimethylformamides In, obtain the Fe that concentration is 80mg/ml3O4/ Polymer nanoparticle suspensions；By 8ml acetonitriles and 8ml N, N- dimethyl methyl Amide is mixed to get the first mixed liquor；Under agitation by 1ml Fe3O4/ Polymer nanoparticle suspensions are added to the first mixing In liquid, and stir to Fe3O4/ Polymer nanoparticles are uniformly dispersed and obtain the second mixed liquor；Under agitation, to the second mixed liquor Middle addition 160mg FeCl3With 160mg isophthalic hypoboric acid and it is uniformly mixing to obtain the 3rd mixed liquor；Under agitation by the 3rd mixing Liquid is warming up to 120 DEG C, and reaction obtains the second reactant liquor in 6 hours, collects the solid product in the second reactant liquor with Magnet afterwards, then Successively with N,N-dimethylformamide to product repeated washing three times (15mL × 3), with ethanol to product repeated washing three times (15mL × 3) and deionized water obtain Fe to product repeated washing three times (15mL × 3)3O4/ Polymer/MOFs composite Nanos Material.
Comparative example
This comparative example is prepared without Fe3O4Metal-organic framework material, first by 320mgFe (NO3)3·9H2O and During 160mg PBA are added to by 8ml acetonitriles and 8ml DMFs, stir complete to ferric nitrate and PBA dissolvings, its It is secondary that resulting solution is transferred in rustless steel politef ethylene reaction kettle, react 3 days in 120 DEG C, then gained is reacted Product collects rufous product in 10000rpm centrifugation 15min, then the rufous product collected is used N, N- dimethyl successively Methanamide is to product repeated washing three times (15mL × 3), with ethanol is to product repeated washing three times (15mL × 3) and uses deionization Washing products therefrom is preferably dried to obtain metal-organic framework material to product repeated washing three times (15mL × 3) by water.
1 structural characterization of experimental example
Fe has successfully been compound in order to probe into macromolecule layer and metal framework MOFs3O4On nanoparticle, this experimental example The Fe is given by embodiment 23O4The Fe obtained in/Polymer/MOFs composite nano materials preparation process3O4Nanoparticle, Fe3O4/ Polymer nanoparticles and Fe3O4The appearance and size of/Polymer/MOFs composite nano materials and microstructure are carried out Characterize as shown in Figures 3 to 8.
(1) pattern and distribution of sizes
From Fig. 3 (A)-(F) as can be seen that Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/Polymer/ MOFs composite nano materials are spherical, and size is homogeneous, and the macromolecule layer and MOF layers wrapped up by data surface does not have to Fe3O4 The pattern of nanoparticle and size produce excessive impact；Fe3O4/ Polymer/MOFs composite nano materials mean diameter is 300nm ～500nm；Fe is obtained by dynamic light scattering detection3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ The mean diameter peak value of Polymer/MOFs composite nano materials is respectively 299 ± 4nm, 317 ± 22nm, 340 ± 61nm (figure 3G-I), this result is consistent with scanning electron microscope and transmission electron microscope results.
(2) microstructure study
As shown in figure 4, Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs is compound to be received Rice material zeta current potentials in deionized water are respectively -15mV (due to Fe3O4The sodium citrate of nanoparticle surface attachment is deposited In carboxyl, so that Fe3O4Nanoparticle shows negative electricity) ,+34mV is (due to Fe3O4After nanoparticle parcel PVP and PEI, PEI is deposited In a large amount of amino, so that Fe3O4/ Polymer nanoparticles show positive electricity) and -12mV (as in MOFs layers, organic ligand PBA is deposited In boric acid base group, so that Fe3O4/ Polymer/MOFs composite nano materials show negative electricity)；This electric charge upset is further proved Macromolecule layer and MOFs layers have successfully been synthesized to Fe3O4Nanoparticle and Fe3O4On/Polymer nanoparticles.
As shown in figure 5, being drawn by Energy Dispersive X-ray (EDX) detection, Fe3O4In nanoparticle, C element weight percent Than for 10.04%, atomic percent be 21.69%, O element weight percents be 31.59%, atomic percent be 51.21%, Fe element weight percents are 58.36%, atomic percent 27.10%；Fe3O4In/Polymer nanoparticles, C element weight It is 14.92% that percentage ratio is 8.20%, atomic percent, and N element percentage by weight is that 12.04%, atomic percent is 18.80%, O element weight percent is that 35.94%, atomic percent is for 49.12%, Fe element weight percents 43.82%th, atomic percent 17.16%；Fe3O4In/Polymer/MOFs composite nano materials, B element percentage by weight is 9.55%th, atomic percent is 16.02%, and it is 18.42% that C element percentage by weight is 12.20%, atomic percent, N element It is that 18.10%, O element weight percents are for 32.88%, atomic percent that percentage by weight is 13.98%, atomic percent 37.27%, Fe element weight percent is 31.39%, atomic percent 10.19%.Can be seen that from above-mentioned testing result Fe3O4There is N element and B element in/Polymer/MOFs composite nano materials, further prove macromolecule layer (in macromolecule layer Contain amino in PEI, in amino, contain N element) and MOFs layers (the organic ligand PBA in MOFs layers contains B element) into Work(is in Fe3O4Nanoparticle surface is formed.
This experimental example using PE spectrometer types fourier transform infrared spectroscopy instrument (FTIR) detect respectively PVP, PEI、PBA、Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials exist 500-4000cm-1Infrared absorption spectroscopy in wave-number range, detection step-length are 4cm-1, testing result is as shown in fig. 6, Fe3O4/ The absworption peak of Polymer/MOFs composite nano materials contains Fe-O (600cm-1)、C-N(1436cm-1) and PBA (633cm-1) Characteristic absorption peak, illustrates the success of macromolecule layer and MOFs layers in Fe3O4Nanoparticle surface is formed.However, C-N and PBA Characteristic peak is weaker, it may be possible to because the reason for content of PVP, PEI and PBA is less.
As shown in fig. 7, by the N for obtaining2The attached isothermal curve of adsorption/desorption shows Fe3O4/ Polymer/MOFs is compound to be received The Langumir surface areas and pore volume of rice material is respectively 159m2/g、0.6cm3/ g, according to Barrett-Joyner-Halenda (BJH) Fe for estimating3O4About 11.8 angstroms～27.3 angstroms of/Polymer/MOFs composite nano materials aperture, the property of this porous Illustrate in Fe3O4/ Polymer nanoparticle surface defines network structure；And the color of product is changed into red from original black Brown, it was demonstrated that this network structure is strictly by Fe3+The metal-organic framework (MOFs) being collectively forming with PBA, Er Feiwu The covalent organic frame (Covalent Organic Frameworks, abbreviation COFs) that only PBA itself dehydrations of color are formed.
This experimental example adopts X ' Pert Pro MPD type X-ray diffraction (XRD) instrument to have detected Fe respectively3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4The X ray diffracting spectrum of/Polymer/MOFs composite nano materials, as shown in figure 8, Fe3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials with standard Fe3O4 Diffraction maximum position consistency, illustrate Fe3O4/ Polymer/MOFs composite nano materials remain Fe3O4The crystal knot of nanoparticle Structure；Meanwhile, Fe3O4/ Polymer/MOFs composite nano materials occur in that a new wide diffraction maximum at 25 °, and comparative example 3 It is resulting without Fe3O4The XRD of metal organic frame product a diffraction maximum is equally existed at 25 °, this illustrate the diffraction maximum be by Occurred in affecting by prepared MOFs shells, the MOFs layers on 2 products therefrom surface of embodiment are by Fe3+Pass through with PBA It is irregular coordination and formed unformed metal-organic framework.
In sum, Fe3O4The shell of/Polymer/MOFs composite nano materials has metal-organic framework, and should Structure does not have a significant effect the magnetic crystal structure of composite nano materials, and this unique MOFs shells are beneficial in glycoprotein Application in capture and release.
2 magnetic property of experimental example is studied
In order to probe into Fe3O4The magnetic property of/Polymer/MOFs composite nano materials, this experimental example adopt STA 449C The Fe that Jupiter type thermogravimetric analysiss (TGA) instrument is given to embodiment 23O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials are warmed up to 850 DEG C of weight loss under nitrogen protection from 35 DEG C, as a result as schemed Shown in 9；Fe is calculated by thermogravimetric analysis data3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ The weight/mass percentage composition (magnetic content) of Polymer/MOFs composite nano materials respectively may be about 83%, 82%, 81%, illustrate Fe3O4 Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials are respectively provided with preferable magnetic Can, it is favorably improved the following protein rate of departure.
Further, this experimental example have detected Fe respectively using Model BHV-525 type vibrating specimen magnetometers (VSM)3O4 Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials arrive 18000Oe -18000 In the range of hysteresis curve (see Figure 10 (A)) and expander graphs of the gained hysteresis curve between -100～100Oe of magnetic field (see Figure 10 (B)), the hysteresis curve of all samples illustrates Fe through origin without remanent magnetism and coercivity3O4Nanoparticle, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials all have superparamagnetism, and prepared Fe3O4Receive Rice corpuscles, Fe3O4/ Polymer nanoparticles, Fe3O4/ Polymer/MOFs composite nano materials magnetic saturation intensities are respectively 64emu/g, 63emu/g, 38emu/g, therefore Fe3O4/ Polymer/MOFs composite nano materials have preferable magnetic responsiveness, Magneto separate (as shown in figure 11) can be completed in 10s.
Application examples glycoprotein Separation Research
Should the Fe that used of use-case3O4/ Polymer/MOFs composite nano materials process standby in accordance with the following methods：Will The Fe that embodiment 2 is obtained3O4/ Polymer/MOFs composite nano materials obtain Fe in being distributed to 1.0mL deionized waters3O4/ Suspension of the Polymer/MOFs composite nano materials concentration for 30mg/mL, it is standby.
Transferrinss (transferrin, TRF) are single chain glycoprotein, its sugar content about 6%, are main in blood plasma containing Iron protein, is responsible for the delivery ferrum absorbed by digestive tube and the ferrum that release is degraded by erythrocyte；It is abnormal in blood to turn ferrum Protein content is relevant with numerous disease, for example heart failure, iron deficiency anemia, malnutrition, atransferrinemia etc..Cause This, should be in use-case, and with transferrinss as model targeting glycoprotein, bovine serum albumin (BSA) is ground for the non-glycoprotein of model Study carefully Selective Separation research of the material to glycoprotein.
Using Fe3O4BR containing acetonitrile (volumetric concentration the be 20%) of/Polymer/MOFs composite nano materials in pH=7 (Britton-Robinson) TRF and the BR in pH=9 in buffer solution (as Incubating Solution) in capture mixed protein system The process of TRF is discharged in buffer solution referring to Fig. 2, operating process is：By transferrinss (TRF), bovine serum albumin (BSA) point It is not dissolved in the BR buffer solution containing acetonitrile (volumetric concentration is 20%) of pH=7, prepared two kinds of concentration are the phase of 1000 μ g/mL Protein solution is answered, and every kind of protein solution equal-volume is uniformly mixed so as to obtain mixed liquid of protein (TRF+BSA)；Take 30 μ L Fe of gained3O4/ The suspension of Polymer/MOFs composite nano materials and 30 μ L mixed liquid of protein, both are mixed in reaction vessel and are incorporated in shake In incubation at room temperature 60min under the conditions of swinging, then separated with Magnet, collect the supernatant and precipitation respectively, then precipitation is used Incubating Solution washs three times (100 μ L every time), is precipitated material.
Deposited material is distributed in 20 μ L Incubating Solutions and is precipitated suspension, take the albumen mixing before 12 μ L incubations respectively Liquid, the supernatant and precipitation suspension carry out SDS-PAGE (SDS-PAGE) analyses, knot Fruit is as shown in figure 12.
The above-mentioned deposited material for being bonded protein is distributed in the BR buffer solution of 40 μ L pH=7 and pH=9 respectively In room temperature elution 60min under the conditions of earthquake, then separated with Magnet, what is obtained after collecting eluent and eluting respectively is heavy Shallow lake material, and the deposited material to obtaining after eluent and eluting carries out SDS-PAGE analyses, as a result as shown in figure 12.
As shown in figure 12, only have BSA remaining in the supernatant, and be bonded the material of albumen and show only TRF bands, say TRF in bright solution has been selectively adsorbed Fe3O4/ Polymer/MOFs composite nano materials surface.When incubating with pH=4 Liquid wash-out protein matter is educated, the glycoprotein TRF for being adsorbed to material surface can not be eluted, and illustrate TRF and Fe3O4/ The combination of Polymer/MOFs composite nano materials is stronger specific binding effect.However, when pH is adjusted to 9, Protein is easily eluted from material surface, illustrates Fe3O4/ Polymer/MOFs composite nano materials being capable of pH responses Property ground reversible must capture and discharge TRF.
As a comparison, the commercial magnetic bead of 900 μ g carboxylations is added to into 30 μ L mixed liquid of protein, by both in reaction vessel In incubation at room temperature 60min under the conditions of mixing earthquake, then separated with Magnet, collected the supernatant and precipitation respectively, Precipitation is washed into three times (100 μ L every time) with Incubating Solution again, material is precipitated.Then deposited material is distributed to into 20 μ L incubations Suspension is precipitated in liquid, the mixed liquid of protein before 12 μ L incubations, the supernatant after incubation after Magneto separate and heavy is taken respectively Shallow lake suspension carries out SDS-PAGE (SDS-PAGE) analyses, as a result as shown in figure 13.Again Above-mentioned deposited material is distributed in the BR buffer solution of 40 μ L pH=7 and pH=9 under the conditions of earthquake respectively in room temperature elution 60min, is then separated with Magnet, the deposited material obtained after collecting eluent and eluting respectively, and to eluent and is washed The deposited material obtained after de- carries out SDS-PAGE analyses, as a result as shown in figure 13.
As shown in figure 13, when the commercial magnetic bead using carboxylation, supernatant include TRF with being bonded on the material of albumen With BSA bands, and it has been bonded the corresponding band of the material of albumen and has become apparent from, has illustrated that commercial magnetic bead has captured protein, but Any selectivity is not shown；And the material for working as the albumen of the BR buffer solution para-linkages with pH=7 and pH=9 is washed When de-, TRF or BSA can not be eluted from commercial magnetic bead by two kinds of eluents, illustrate that commercial magnetic bead does not show pH Response performance.
Transferrinss that should be in use-case could alternatively be the sugar such as horseradish peroxidase (HRP) or alpha-fetoprotein (AFP) Albumen；Bovine serum albumin (BSA) could alternatively be lysozyme (LYZ), Chymotrypsin (CTP), cytochrome C (Cyt C) etc. Non- glycoprotein, and above-mentioned glycoprotein and non-glycoprotein can be arranged in pairs or groups with arbitrary proportion.
The BR buffer solution containing acetonitrile (volumetric concentration is 20%) of the pH=7 that should be adopted in use-case could alternatively be pH =7 disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution containing acetonitrile (volumetric concentration is 20%), or pH=7 containing acetonitrile (volume Concentration is dipotassium hydrogen phosphate-potassium phosphate buffer 20%)；Using the BR buffer solution of pH=9 could alternatively be pH For 8～9 glycine-sodium hydrate buffer solution, or Tris-hydrochloride buffer.
In a word, prepared Fe3O4/ CMCS/PAAPBA nanospheres can be with pH responsively to glycoprotein in biological specimen Selectivity is captured, and is enriched with and is discharged, and illustrates its application potential in diagnosis and protein science.
One of ordinary skill in the art will be appreciated that embodiment here is to aid in the reader understanding present invention's Principle, it should be understood that protection scope of the present invention is not limited to such especially statement and embodiment.This area it is common Technical staff can make various other various tools without departing from essence of the invention according to these technology enlightenments disclosed by the invention Body deforms and combines, and these deformations and combination are still within the scope of the present invention.

Claims (10)

1.pH response type magnetic metal organic frame composite nano materials, it is characterised in that the composite nano materials are by Fe3O4Nanometer Particle, is coated on Fe3O4The macromolecule layer of nanoparticle surface and the metal organic frame being grown on macromolecule layer are constituted； First polymer or first polymer and hydrophilic by chelated metal ions of the macromolecule layer for chelated metal ions Second polymer composition, when macromolecule layer is by the first polymer and hydrophilic second polymer group of chelated metal ions Cheng Shi, the first polymer are 1 with the mass ratio of second polymer：(0.3～1)；The metal organic frame is by Fe3+With Phenyl boronic acid derivative containing at least one carboxyl or at least two boronates is by being coordinated bond formed.
2. pH response types magnetic metal organic frame composite nano materials according to claim 1, it is characterised in that described One polymer is polyvinylpyrrolidone or poly-dopamine；The second polymer is Polyetherimide or polyacrylic acid.
3. pH response types magnetic metal organic frame composite nano materials according to claim 1, it is characterised in that described to contain Have at least one carboxyl phenyl boronic acid derivative be 5- boronate M-phthalic acids, 3- Carboxybenzeneboronic acids or 4- Carboxybenzeneboronic acids, The phenyl boronic acid derivative containing at least two boronates is to benzene hypoboric acid or isophthalic hypoboric acid.
4. pH response types magnetic metal organic frame composite nano materials according to any claim in claims 1 to 3, It is characterized in that the mean diameter of the composite nano materials is 300nm～500nm.
5. pH response types magnetic metal organic frame composite nano materials described in any claim in a kind of Claims 1-4 Preparation method, it is characterised in that step is as follows：
(1) prepare Fe3O4Nanoparticle suspension and water-soluble polymers
By Fe3O4Nanoparticle is distributed in deionized water, prepares Fe3O4Nanoparticle concentration is the Fe of 40～80mg/mL3O4Receive Rice corpuscles suspension；First polymer or first polymer are dissolved in deionized water with second polymer, first are prepared and is polymerized Thing concentration is 55～85mg/ml or first polymer and the water-soluble polymers that second polymer total concentration is 55～85mg/ml, When first polymer is dissolved in deionized water with second polymer, first polymer is 1 with the mass ratio of second polymer： (0.3～1)；
(2) prepare Fe3O4/ Polymer nanoparticles
The Fe that step (1) is prepared3O4Nanoparticle suspension and water-soluble polymers are according to volume ratio 1：(2～6) are measured and are added Enter in reaction vessel, the first reactant liquor is obtained within least 8 hours in room temperature reaction under agitation, then collect first with Magnet and react Solid product in liquid, then deionized water, ethanol and DMF obtain Fe to solid product washing successively3O4/ Polymer nanoparticles；
(3) pH response type magnetic metal organic frame composite nano materials are prepared
By the Fe after washing obtained by step (2)3O4/ Polymer nanoparticles are distributed in DMF, obtain dense Spend the Fe for 65～95mg/ml3O4/ Polymer nanoparticle suspensions；Acetonitrile and N,N-dimethylformamide equal-volume are mixed Conjunction uniformly obtains the first mixed liquor；By Fe3O4/ Polymer nanoparticle suspensions and N in the first mixed liquor, N- dimethyl formyls The volume ratio of amine is that 1 ︰ (1～16) measures Fe3O4/ Polymer nanoparticle suspensions and the first mixed liquor, under agitation will Fe3O4/ Polymer nanoparticle suspensions are added in the first mixed liquor, and are stirred to Fe3O4/ Polymer nanoparticles point Dissipate and uniformly obtain the second mixed liquor；Under agitation, add in the second mixed liquor and solubility trivalent iron salt and contain at least one The phenyl boronic acid derivative of carboxyl or at least two boronates is simultaneously uniformly mixing to obtain the 3rd mixed liquor, the phenyl boronic acid derivative Addition on the basis of the content of DMF in the second mixed liquor, per 6～10ml DMFs 1 mM of phenyl boronic acid derivative is added, the solubility trivalent iron salt is (0.5～2) with the mol ratio of phenyl boronic acid derivative:1； The 3rd mixed liquor is warming up to into 100～130 DEG C of reactions under agitation and obtains the second reactant liquor within least 1 hour, received with Magnet afterwards Collect the solid product in the second reactant liquor, then solid product is washed with DMF, ethanol and deionized water successively Wash.
6. the preparation method of pH response types magnetic metal organic frame composite nano materials according to claim 5, its feature It is the Fe3O4Nanoparticle is prepared by the following method and obtains：By raw material iron chloride, sodium citrate and ammonium acetate by mole Than 1:(0.33～0.79):10 are added in the reaction vessel of the solvent ethylene glycol for filling chlorination weight of iron (33～36) times, Each material dissolution mix homogeneously are made under stirring, is then reacted at least 15 hours at 180～220 DEG C, reaction will reaction after terminating Liquid temp is down to room temperature, collects the Fe in reactant liquor with Magnet3O4Nanoparticle, then uses ethanol, deionized water pair successively Fe3O4Nanoparticle carries out washing and removes unreacted raw material.
7. according to claim 5 or 6 pH response types magnetic metal organic frame composite nano materials preparation method, which is special Levy is that the first polymer is polyvinylpyrrolidone or poly-dopamine；The second polymer is Polyetherimide Or polyacrylic acid；The solubility trivalent iron salt is Fe (NO)3Or FeCl3；The phenylboric acid containing at least one carboxyl derives Thing be 5- boronate M-phthalic acids, 3- Carboxybenzeneboronic acids or 4- Carboxybenzeneboronic acids, the benzene containing at least two boronates Boronic acid derivatives are to benzene hypoboric acid or isophthalic hypoboric acid.
8. in Claims 1-4 pH response types magnetic metal organic frame composite nano materials described in any claim in sugar Application during albumen is captured or glycoprotein discharges.
9. application according to claim 8, it is characterised in that in the case where pH is for neutral environment, the magnetic metal organic frame Composite nano materials realize the capture to glycoprotein；Under the alkaline environment of pH=8～9, the magnetic metal organic frame is multiple Nano material is closed by the glycoprotein release for capturing.
10. application according to claim 8, it is characterised in that the glycoprotein is transferrinss, horseradish peroxidase Or alpha-fetoprotein.
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