CN117225385B - Preparation method and application of surface modified porous oxide chromatographic material - Google Patents
Preparation method and application of surface modified porous oxide chromatographic material Download PDFInfo
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- CN117225385B CN117225385B CN202311498997.3A CN202311498997A CN117225385B CN 117225385 B CN117225385 B CN 117225385B CN 202311498997 A CN202311498997 A CN 202311498997A CN 117225385 B CN117225385 B CN 117225385B
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- 239000000463 material Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
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- 238000000576 coating method Methods 0.000 claims abstract description 17
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- 238000001914 filtration Methods 0.000 claims description 10
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- 238000001291 vacuum drying Methods 0.000 claims description 7
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003636 chemical group Chemical group 0.000 claims description 6
- 238000004811 liquid chromatography Methods 0.000 claims description 6
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- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 4
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 claims description 4
- 229950000244 sulfanilic acid Drugs 0.000 claims description 4
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- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
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- 239000001656 lutein Substances 0.000 claims description 3
- 229960005375 lutein Drugs 0.000 claims description 3
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 claims description 3
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 claims description 3
- 235000010199 sorbic acid Nutrition 0.000 claims description 3
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 claims description 3
- UKRDPEFKFJNXQM-UHFFFAOYSA-N vinylsilane Chemical compound [SiH3]C=C UKRDPEFKFJNXQM-UHFFFAOYSA-N 0.000 claims description 3
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 claims description 3
- GXDPEHGCHUDUFE-UHFFFAOYSA-N sulfanylmethanol Chemical compound OCS GXDPEHGCHUDUFE-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 239000003513 alkali Substances 0.000 abstract description 9
- 125000005647 linker group Chemical group 0.000 abstract description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 12
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- 238000012360 testing method Methods 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 3
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- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
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- MBMBGCFOFBJSGT-KUBAVDMBSA-N docosahexaenoic acid Natural products CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 1
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Abstract
The invention discloses a preparation method and application of a surface modified porous oxide chromatographic material, wherein a sulfhydryl group is introduced into the surface of the porous oxide material, then an excessive organic matter containing a plurality of double bonds is coupled to the sulfhydryl group through click reaction, and then the excessive organic matter containing a plurality of sulfhydryl groups and the residual double bonds of the organic matter containing a plurality of double bonds are subjected to click reaction again, so that new sulfhydryl groups are introduced. The above process is repeated a plurality of times to obtain a modified organic coating on the surface of the porous oxide material. The coating can protect the surface of the porous oxide material, effectively prevent salt or alkaline groups from damaging bonding groups on the surface of the porous oxide material, and ensure that the modified chromatographic material has better service life under the conditions of high salt and high alkali.
Description
Technical Field
The invention relates to the technical field of biological medicine, in particular to a preparation method and application of a surface modified porous oxide chromatographic material.
Background
In the biomedical field, it is often necessary to separate the target substance from impurities in order to obtain the target drug or an intermediate thereof in high purity. In this process, the chromatographic separation technique and the critical chromatographic separation material are not separated. In chromatographic separation, high molecular polymer materials and metal or non-metal oxide materials are most widely used. The high polymer material represented by polystyrene divinylbenzene resin has the advantages of alkali resistance and salt resistance, can be used in some harsh chromatographic mobile phase environments, but has lower mechanical strength, complex pore structure and unsatisfactory effect when separating some mixtures with similar structures. The porous oxide material represented by silica gel has higher mechanical strength, adjustable and optimized pore structure and better separation effect, but can not work in a high-salt high-alkali mobile phase environment.
In order to realize the advantages of compatible high molecular polymer materials and porous oxide materials, attempts may be made to introduce a high molecular polymer coating on the surface of the porous oxide material. In the prior art, organosilane is introduced into a silica gel skeleton or surface for hybridization, and then C18 silane is bonded, so that the modified porous silica gel chromatographic material capable of tolerating a mobile phase with pH of 12.5 is obtained, but the material does not form a high-molecular polymer coating, the surface of the material is not covered to a sufficient extent, the mobile phase with higher pH value (such as pH 13) cannot be tolerated, and in the mobile phase with high salt, the C18 bonding compatibility is easy to run off. However, the ethylene double bond of the crosslinking agent is easier to generate self-polymerization in the reaction solution, particles are formed on the surface of the material, pore channels of the porous material are blocked, and the chromatographic performance of the obtained material is poor.
Disclosure of Invention
The invention aims to solve the technical problems of overcoming the defects in the prior art and providing a preparation method and application of a surface modified porous oxide chromatographic material, wherein an organic coating is formed on the surface of the porous oxide material through repeated reaction of sulfhydryl groups and double bond groups, and the organic coating can protect the surface of the porous oxide material, and is not easy to run off because the coating is formed by crosslinking, so that the porous oxide chromatographic material can resist mobile phases with high salt and high alkali.
The invention is realized by the following technical scheme:
the preparation method of the surface modified porous oxide chromatographic material is characterized by comprising the following steps of:
s1, introducing a sulfhydryl group on the surface of a porous oxide material to obtain a porous oxide bonded with the sulfhydryl group;
s2, coupling excessive organic matters containing multiple double bonds with mercapto groups on the surface of the porous oxide bonded with the mercapto groups through click reaction to obtain a porous oxide modified with double bonds;
s3, reacting residual double bonds in the porous oxide with modified double bonds with excessive organic matters containing a plurality of mercapto groups to obtain porous oxide with modified mercapto groups again;
s4, repeating the steps S2 and S3, and forming a crosslinked organic coating on the surface of the porous oxide material;
s5, modifying specific chemical groups on the organic coating to obtain the porous oxide chromatographic material.
According to the above technical solution, preferably, step S1 includes: mixing porous oxide material, toluene and mercaptosilane; filtering out the modified porous oxide material after reflux reaction; and vacuum drying to obtain the porous oxide bonded with mercapto.
According to the above technical solution, preferably, step S1 includes: mixing porous oxide material, toluene and vinyl silane; filtering out the modified porous oxide material after reflux reaction; vacuum drying to obtain porous oxide bonded with vinyl; mixing the vinyl-bonded porous oxide, toluene, azobisisobutyronitrile, dimercaptopropanol; filtering out the modified porous oxide bonded with vinyl after reflux reaction; and vacuum drying to obtain the porous oxide bonded with mercapto.
According to the above technical scheme, preferably, the porous oxide material is full porous silica gel, hybrid core-shell silica gel, alumina, zirconia or a mixture of any proportion thereof.
According to the above technical solution, preferably, step S2 includes: adding the porous oxide bonded with the mercapto, methanol, excessive organic matters containing multiple double bonds and azodiisobutyl cyanide for click reaction; filtering out the reaction product to obtain the porous oxide with modified double bond.
According to the above technical scheme, in step S2, preferably, the organic matter containing multiple double bonds includes one of 2, 4-hexadienoic acid, polyunsaturated fatty acid, lutein or its corresponding ester or amide derivatives, and may be a mixture of the above materials in any proportion.
According to the above technical solution, preferably, step S3 includes: sequentially adding the porous oxide with modified double bonds, excessive organic matters containing a plurality of mercapto groups, methanol and azodiisobutyl cyanide for reaction; the reaction product is filtered out to obtain the porous oxide modified with sulfhydryl.
According to the above technical solution, preferably, in step S3, the organic matter containing multiple mercapto groups includes one of dimercaptopropanol and trimercapto S-triazine or a mixture of any proportion.
According to the above technical scheme, in step S5, preferably, one of the specific chemical groups of octadecylamine, sulfanilic acid and ethylenediamine or a mixture of any proportions is used.
The patent also discloses an application of the surface modified porous oxide chromatographic material, and the porous oxide chromatographic material can be used for mobile phase conditions of high-concentration salt with the pH value not lower than 50mM in liquid chromatography or can be used for mobile phase conditions of high-alkali with the pH value not lower than 13 in liquid chromatography based on the preparation method of the surface modified porous oxide chromatographic material.
The beneficial effects of the invention are as follows:
the invention can modify organic molecules step by step through repeated reaction of sulfhydryl and double bond groups, form a cross-linked network structure, cover the surface of porous oxide, and form a protective layer, wherein the coating can prevent salt or alkaline groups from damaging bonding groups on the surface of the porous oxide material, so that the modified chromatographic material has better service life under high salt and high alkali conditions, and meanwhile, different groups can be modified through specific chemical reaction to obtain corresponding adsorption performance.
Drawings
FIG. 1 is an infrared test chart of a porous oxide material (e.g., silica gel) of the present invention.
FIG. 2 is an infrared test chart of a porous oxide having a mercapto group bonded thereto (silica gel modified with a mercapto group) according to the present invention.
FIG. 3 is an infrared test chart of a porous oxide modified with double bonds (material obtained by modifying polyunsaturated fatty acids with mercaptosilica gel) according to the present invention.
FIG. 4 is a test chromatogram before washing a 4.6X250 mm specification column packed with C18 modified organic coated silica gel in example 10 using a 100mmol/L sodium hydroxide (pH 13) solution containing 5% methanol for 100 hours.
FIG. 5 is a test chromatogram after washing a 4.6X250 mm specification column packed with C18 modified organic coated silica gel in example 10 with 100mmol/L sodium hydroxide (pH 13) solution containing 5% methanol for 100 hours.
Detailed Description
The present invention will be described in further detail below with reference to the drawings and preferred embodiments, so that those skilled in the art can better understand the technical solutions of the present invention. All other embodiments, based on the embodiments of the invention, which would be apparent to one of ordinary skill in the art without making any inventive effort are intended to be within the scope of the invention.
As shown, the present invention includes the steps of:
s1, introducing sulfhydryl groups on the surface of a porous oxide material to obtain the porous oxide bonded with sulfhydryl groups, wherein the porous oxide material is silica gel, hybrid core-shell silica gel, alumina, zirconia or a mixture of any proportion thereof.
Example 1: 10g of 5 μm silica gel was sequentially added to a 250ml reaction vessel, 100ml of toluene was added, 5g of mercaptosilane was added, followed by stirring, reflux reaction was performed for 16 hours, and the modified silica gel was filtered off and dried under vacuum at 95℃for 16 hours to obtain mercapto-bonded silica gel.
Example 2: 10g of 5 μm hybrid silica gel was sequentially added to a 250ml reaction vessel, 100ml of toluene was added, 5g of mercaptosilane was added, followed by stirring, reflux reaction was performed for 16 hours, and the modified silica gel was filtered off and dried under vacuum at 95℃for 16 hours to obtain mercapto-bonded hybrid silica gel.
Example 3: 10g of 5 mu m hybridized core-shell silica gel is sequentially added into a 250ml reaction kettle, 100ml of toluene is added, 5g of mercaptosilane is added, then stirring is carried out, the modified silica gel is filtered out after 16 hours of reflux reaction, and the modified silica gel is dried in vacuum at 95 ℃ for 16 hours to obtain the mercapto-bonded hybridized core-shell silica gel.
Example 4: 10g of 40 μm alumina was sequentially added to a 250ml reaction vessel, 100ml of toluene was added, 5g of mercaptosilane was added, followed by stirring, reflux reaction was performed for 16 hours, and the modified alumina was filtered off and dried under vacuum at 95℃for 16 hours to obtain alumina bonded with mercapto groups.
Example 5: 10g of 10 μm zirconia was sequentially added to a 250ml reaction vessel, 100ml of toluene was added, 5g of mercaptosilane was added, followed by stirring, reflux reaction was performed for 16 hours, and the modified zirconia was filtered off and dried under vacuum at 95℃for 16 hours to obtain mercapto-bonded zirconia.
Example 6: sequentially adding 10g of 5 mu m silica gel into a 250ml reaction kettle, adding 100ml of toluene, adding 5g of vinyl silane, stirring, carrying out reflux reaction for 16 hours, filtering out modified silica gel, and carrying out vacuum drying at 95 ℃ for 16 hours to obtain vinyl-bonded silica gel; the bonded vinyl silica gel is placed in a 250ml reaction kettle, 100ml of toluene, 200mg of azobisisobutyronitrile and 5g of dimercaptopropanol are added, then the mixture is stirred, the modified silica gel is filtered out after 16 hours of reflux reaction, and the modified silica gel is dried in vacuum at 95 ℃ for 16 hours to obtain the bonded mercapto silica gel.
And S2, coupling excessive organic matters containing multiple double bonds with mercapto groups on the surface of the porous oxide bonded with the mercapto groups through click reaction to obtain the porous oxide modified with the double bonds. The organic matter containing multiple double bonds is preferably but not limited to one of 2, 4-hexadienoic acid, polyunsaturated fatty acid (such as linolenic acid, linoleic acid, DHA, EPA) and lutein or its corresponding ester or amide derivatives, and can be mixture of the above materials in any proportion.
Example 7: 10g of the porous oxide bonded with the mercapto group (taking silica gel bonded with the mercapto group as an example), 100mL of methanol, 5g of organic matters containing a plurality of double bonds (taking linolenic acid as an example) and 200mg of azodiisobutyl cyanide are added into a 250mL reaction kettle to carry out click reaction; the reaction is carried out for 16 hours at 60 ℃, and the reaction product is filtered out to obtain the porous oxide with modified double bonds.
S3, reacting residual double bonds in the porous oxide with modified double bonds with an organic matter containing a plurality of sulfhydryl groups. Wherein the organic matter containing multiple mercapto groups is preferably, but not limited to, one of dimercaptopropanol and trimercapto s-triazine or a mixture of any proportion.
Example 8: 10g of porous oxide with modified double bonds, 10g of organic matters containing a plurality of mercapto groups (taking dimercaptopropanol as an example), 100mL of methanol and 200mg of azodiisobutyl cyanide are sequentially added into a 250mL reaction kettle to react; the reaction is carried out for 16 hours at 60 ℃, and the reaction product is filtered out to obtain the porous oxide with modified sulfhydryl.
S4, repeating the steps S2 and S3 to form a crosslinked organic coating on the surface of the porous oxide material, wherein the repetition number of the repeated reaction is preferably 1-30 times.
Example 9: in a 250mL reaction kettle, 10g of the mercapto-modified porous oxide obtained in example 8, 100mL of methanol, 5g of organic matter containing a plurality of double bonds (in the case of linolenic acid) and 200mg of azodiisobutyl cyanide are taken for reaction; reacting at 60 ℃ for 16 hours, filtering out a reaction product to obtain the porous oxide with the repeated modified double bonds; then 10g of organic matter containing a plurality of mercapto groups (taking dimercaptopropanol as an example) and 100mL of methanol are added to react with 200mg of azodiisobutyl cyanide; the reaction is carried out for 16 hours at 60 ℃, the reaction product is filtered out, and after repeated reaction for a plurality of times, a crosslinked organic coating is formed on the surface of the porous oxide material.
S5, the organic matter coating has modifiable sites such as alcoholic hydroxyl groups and carboxyl groups, and can allow specific chemical groups such as reversed-phase groups and ion exchange groups to be introduced, so that modified chromatographic materials with different adsorption performances are obtained. Wherein the specific chemical group is one of octadecylamine, sulfanilic acid and ethylenediamine or a mixture of any proportion. As can be seen from FIGS. 1 to 3, FIG. 1 is an infrared test chart of silica gel, FIG. 2 is an infrared test chart of mercapto-modified silica gel, wherein 2591.40cm -1 The infrared absorption characteristic peaks of the mercapto group are shown in FIG. 3, which is an infrared test chart of the material obtained by modifying polyunsaturated fatty acids with mercapto silica gel, wherein 1728.03cm -1 The infrared absorption characteristic peak of carboxyl is shown, the infrared absorption characteristic peak corresponding to sulfhydryl is disappeared, and the process of gradually modifying sulfhydryl and carboxyl on the silica gel is shown in figures 1-3.
Example 10: 10g of the modified organic-coated silica gel of example 9 was charged into a 250ml reaction vessel containing 100ml of N, N-Dimethylformamide (DMF), followed by 10g of N-hydroxysuccinimide (NHS), 5g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 5g of octadecylamine, and reacted at normal temperature for 48 hours to obtain a C18-modified organic-coated silica gel.
Example 11: 10g of the modified organic-coated silica gel of example 9 was taken, added to a 250ml reaction vessel containing 100ml of DMF, and then 10g of NHS, 5g of EDC and 5g of sulfanilic acid were added to react at room temperature for 48 hours to obtain a sulfonic acid group-modified organic-coated silica gel.
Example 12: 10g of the modified organic-coated silica gel of example 9 was taken, added to a 250ml reaction vessel containing 100ml of DMF, and then 10g of NHS, 5g of EDC and 5g of ethylenediamine were added to react at room temperature for 48 hours to obtain an amino-modified organic-coated silica gel.
Example 13: the patent also discloses an application of the surface modified porous oxide chromatographic material, and the porous oxide chromatographic material can be used for mobile phase conditions of high-concentration salt with the pH value not lower than 50mM in liquid chromatography or can be used for mobile phase conditions of high-alkali with the pH value not lower than 13 in liquid chromatography based on the preparation method of the surface modified porous oxide chromatographic material.
Taking example 10 as an example, the C18 modified organic coated silica gel of example 10 was packed into a 4.6 x 250mm column and then rinsed with a 5% methanol solution of 100mmol/L sodium hydroxide (pH 13) at 40 ℃ for 100 hours. The change in retention time of naphthalene by the column before and after washing was compared with naphthalene as an index. Wherein, FIGS. 4-5 are test chromatograms before and after washing a C18 modified organic coated silica gel packed in example 10 with 100mmol/L sodium hydroxide (pH 13) solution containing 5% methanol, respectively, showing naphthalene retention time before washing of 5.518min and naphthalene retention time after washing of 5.476min. The change is less than 5%, which proves that the chromatographic material has better alkali resistance and salt resistance.
Chromatographic conditions for testing naphthalene retention time were: methanol-water=60:40 is used as a mobile phase, the flow rate is 1.0mL/min, the test samples are methanol solutions of uracil, phenol, nitrobenzene and naphthalene, the concentrations are 500ppm, the sample injection amount is 1 mu L, the column temperature is 25 ℃, and the detection wavelength is as follows: 254nm.
The technical principle of the invention is as follows: the mercapto-double bond reaction based on click chemistry, because the reactive groups of the two reagents participating in the reaction are different, unlike the reaction of the two reagents participating in the ethylene double bond copolymerization reaction, the mercapto-double bond reaction can avoid the problem of self-polymerization; and the thioether bond formed by the reaction is an inert group, so that a coating with better protection performance can be formed.
The invention can modify organic molecules step by step through repeated reaction of sulfhydryl and double bond groups, form a cross-linked network structure, cover the surface of porous oxide, and form a protective layer, wherein the coating can prevent salt or alkaline groups from damaging bonding groups on the surface of the porous oxide material, so that the modified chromatographic material has better service life under high salt and high alkali conditions, and meanwhile, different groups can be modified through specific chemical reaction to obtain corresponding adsorption performance.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (6)
1. The preparation method of the surface modified porous oxide chromatographic material is characterized by comprising the following steps of:
s1, introducing a sulfhydryl group on the surface of a porous oxide material to obtain a porous oxide bonded with the sulfhydryl group; the porous oxide material is full porous silica gel, hybrid core-shell silica gel, alumina, zirconia or a mixture of any proportion thereof;
s2, coupling excessive organic matters containing multiple double bonds with mercapto groups on the surface of the porous oxide bonded with the mercapto groups through click reaction to obtain a porous oxide modified with double bonds; the organic matter containing multiple double bonds is selected from one of 2, 4-hexadienoic acid, polyunsaturated fatty acid and lutein or corresponding ester or amide derivatives thereof, or a mixture of the above substances in any proportion;
s3, reacting residual double bonds in the porous oxide with modified double bonds with excessive organic matters containing a plurality of mercapto groups to obtain porous oxide with modified mercapto groups again; the organic matter containing a plurality of mercapto groups is selected from one or a mixture of any proportion of dimercaptopropanol and trimercapto-s-triazine;
s4, repeating the steps S2 and S3, and forming a crosslinked organic coating on the surface of the porous oxide material;
s5, modifying specific chemical groups on the organic matter coating to obtain the porous oxide chromatographic material, wherein the specific chemical groups are one or a mixture of any proportion of octadecylamine, sulfanilic acid and ethylenediamine.
2. The method for preparing a surface-modified porous oxide chromatographic material of claim 1, wherein step S1 comprises: mixing porous oxide material, toluene and mercaptosilane; filtering out the modified porous oxide material after reflux reaction; and vacuum drying to obtain the porous oxide bonded with mercapto.
3. The method for preparing a surface-modified porous oxide chromatographic material of claim 1, wherein step S1 comprises: mixing porous oxide material, toluene and vinyl silane; filtering out the modified porous oxide material after reflux reaction; vacuum drying to obtain porous oxide bonded with vinyl; mixing the vinyl-bonded porous oxide, toluene, azobisisobutyronitrile, dimercaptopropanol; filtering out the modified porous oxide bonded with vinyl after reflux reaction; and vacuum drying to obtain the porous oxide bonded with mercapto.
4. The method for preparing a surface-modified porous oxide chromatographic material of claim 1, wherein step S2 comprises: adding the porous oxide bonded with the mercapto, methanol, excessive organic matters containing multiple double bonds and azodiisobutyl cyanide for click reaction; filtering out the reaction product to obtain the porous oxide with modified double bond.
5. The method for preparing a surface-modified porous oxide chromatographic material of claim 4, wherein step S3 comprises: sequentially adding the porous oxide with modified double bonds, excessive organic matters containing a plurality of mercapto groups, methanol and azodiisobutyl cyanide for reaction; the reaction product is filtered off to obtain a porous oxide with the mercapto group modified again.
6. Use of the surface-modified porous oxide chromatographic material obtained by the process according to any of claims 1-5 for mobile phase conditions of high concentration salt of not less than 50mM in liquid chromatography or for mobile phase conditions of high base of not less than 13 in liquid chromatography.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104689807A (en) * | 2013-12-04 | 2015-06-10 | 中国科学院大连化学物理研究所 | Am imidazole dicationic ionic liquid hydrophilic interaction chromatography stationary phase, and preparation and applications thereof |
| CN104707568A (en) * | 2013-12-13 | 2015-06-17 | 中国科学院大连化学物理研究所 | Porous monolithic material for chromatographic separation, and preparation method and application thereof |
| CN107126943A (en) * | 2017-05-25 | 2017-09-05 | 华东理工大学 | Phenyl boric acid modified silica-gel function chromatograph packing material, preparation method and application |
| CN107138144A (en) * | 2017-05-25 | 2017-09-08 | 华东理工大学 | A kind of hydrophilic chromatographic filler, its preparation method and the application of hybrid ionic switch mode |
| CN109865315A (en) * | 2017-12-05 | 2019-06-11 | 中国科学院大连化学物理研究所 | A kind of organic-inorganic hybrid mesoporous material coating preparation method as chromatographic stationary phases |
| CN109865507A (en) * | 2017-12-05 | 2019-06-11 | 中国科学院大连化学物理研究所 | A kind of novel silica gel stromal surface method of modifying and its application |
| RU2753408C1 (en) * | 2020-10-07 | 2021-08-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный университет" (ФГБОУ ВО "КубГУ") | Method for producing silica gel with immobilized aldehyde group |
| CN115178245A (en) * | 2022-06-21 | 2022-10-14 | 南通裕弘分析仪器有限公司 | Preparation method and application of organic-inorganic hybrid silica gel particles |
-
2023
- 2023-11-13 CN CN202311498997.3A patent/CN117225385B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104689807A (en) * | 2013-12-04 | 2015-06-10 | 中国科学院大连化学物理研究所 | Am imidazole dicationic ionic liquid hydrophilic interaction chromatography stationary phase, and preparation and applications thereof |
| CN104707568A (en) * | 2013-12-13 | 2015-06-17 | 中国科学院大连化学物理研究所 | Porous monolithic material for chromatographic separation, and preparation method and application thereof |
| CN107126943A (en) * | 2017-05-25 | 2017-09-05 | 华东理工大学 | Phenyl boric acid modified silica-gel function chromatograph packing material, preparation method and application |
| CN107138144A (en) * | 2017-05-25 | 2017-09-08 | 华东理工大学 | A kind of hydrophilic chromatographic filler, its preparation method and the application of hybrid ionic switch mode |
| CN109865315A (en) * | 2017-12-05 | 2019-06-11 | 中国科学院大连化学物理研究所 | A kind of organic-inorganic hybrid mesoporous material coating preparation method as chromatographic stationary phases |
| CN109865507A (en) * | 2017-12-05 | 2019-06-11 | 中国科学院大连化学物理研究所 | A kind of novel silica gel stromal surface method of modifying and its application |
| RU2753408C1 (en) * | 2020-10-07 | 2021-08-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кубанский государственный университет" (ФГБОУ ВО "КубГУ") | Method for producing silica gel with immobilized aldehyde group |
| CN115178245A (en) * | 2022-06-21 | 2022-10-14 | 南通裕弘分析仪器有限公司 | Preparation method and application of organic-inorganic hybrid silica gel particles |
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