WO2017110819A1 - Agent de séparation pour chromatographie, colonne chromatographique, et procédé de séparation par chromatographie - Google Patents

Agent de séparation pour chromatographie, colonne chromatographique, et procédé de séparation par chromatographie Download PDF

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WO2017110819A1
WO2017110819A1 PCT/JP2016/087973 JP2016087973W WO2017110819A1 WO 2017110819 A1 WO2017110819 A1 WO 2017110819A1 JP 2016087973 W JP2016087973 W JP 2016087973W WO 2017110819 A1 WO2017110819 A1 WO 2017110819A1
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chromatography
sample
diamine
group
separation
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PCT/JP2016/087973
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English (en)
Japanese (ja)
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興祐 福澤
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信和化工株式会社
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Priority to JP2017522567A priority Critical patent/JP6368430B2/ja
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86

Definitions

  • the present invention relates to a separation agent for chromatography, a chromatography column, and a separation method by chromatography.
  • a chromatographic separation agent is a material that functions as a stationary phase by being packed or formed in a chromatography column.
  • Silica gel is widely used as such a chromatographic separating agent. Silica gel has the advantages of high physical strength and large specific surface area.
  • Patent Document 1 US2013 / 0319086A1
  • Patent Document 2 US2012 / 0273404A1
  • Patent Document 3 disclose a separating agent in which a hydrophobic group and an ionic group are immobilized on silica gel, and the ionic group is mediated by an alkylene group. It is described that it may contain an amino group modified with an amino group or an alkyl group.
  • Patent Document 3 US Pat. No.
  • Patent Document 4 discloses a separating agent in which a diamine is immobilized on silica gel via a short-chain alkylene group.
  • Patent Document 4 discloses a separating agent in which polyamine is immobilized on silica gel.
  • Patent Document 5 discloses a separating agent in which a diamine is immobilized on silica gel via a short-chain alkylene group.
  • Patent Document 7 discloses a separating agent synthesized by reacting an anthracene having an amino group with an epoxide modified on silica gel in order to immobilize anthracene on silica gel. It is understood that this separating agent separates unsaturated compounds not by amino group interactions but by terminal aromatic ring interactions.
  • the present inventor has recently modified the surface of a porous base material with a silane functional group containing an aromatic ring modified with a diamine, and interposing the aromatic ring between the porous base material and the diamine.
  • the present inventors have found that chromatographic separation agents that are generally excellent in separation performance such as holding power can be provided.
  • an object of the present invention is to provide a chromatographic separation agent that is generally excellent in separation performance such as selectivity and holding power.
  • the porous base material is surface-modified with a silane functional group containing an aromatic ring modified with a diamine, and the aromatic ring is interposed between the porous base material and the diamine.
  • a chromatographic separation agent is provided.
  • a chromatography column comprising a cylindrical column body and the chromatographic separation agent packed or formed in the column body.
  • a chromatographic separation method including a step of separating a plurality of substances using the chromatographic separation agent.
  • FIG. 2 is a chromatogram obtained by performing separation in HILIC mode on the sample 1 using the separation agent obtained in Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation in Sample 1 on a HILIC mode using the separation agent obtained in Comparative Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation on sample 2 in HILIC mode using the separation agent obtained in Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation in Sample 2 on a HILIC mode using the separating agent obtained in Comparative Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation on sample 3 in HILIC mode using the separation agent obtained in Example 1.
  • FIG. 3 is a chromatogram obtained by performing separation in HILIC mode using the separation agent obtained in Comparative Example 1 on Sample 3.
  • FIG. 2 is a chromatogram obtained by performing separation in Sample 4 on a HILIC mode using the separation agent obtained in Example 1.
  • FIG. 3 is a chromatogram obtained by performing separation in Sample 4 on a HILIC mode using the separation agent obtained in Comparative Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation on sample 5 in HILIC mode using the separation agent obtained in Example 1.
  • FIG. 6 is a chromatogram obtained by performing separation in Sample 5 on a HILIC mode using the separating agent obtained in Comparative Example 1.
  • FIG. 2 is a chromatogram obtained by performing separation on a sample 6 in HILIC mode using the separation agent obtained in Example 1.
  • FIG. FIG. 6 is a chromatogram obtained by performing separation in Sample 6 on a HILIC mode using the separation agent obtained in Comparative Example 1.
  • FIG. 4 is a chromatogram obtained by performing separation in HILIC mode using the separation agent obtained in Example 1 on Sample 7.
  • FIG. 7 is a chromatogram obtained by performing separation in HILIC mode using the separation agent obtained in Comparative Example 1 on Sample 7.
  • FIG. 2 is a chromatogram obtained by performing separation on a sample 8 in HILIC mode using the separation agent obtained in Example 1.
  • FIG. 6 is a chromatogram obtained by performing separation in Sample 8 on a HILIC mode using the separating agent obtained in Comparative Example 1.
  • FIG. It is a graph which shows the evaluation result of the stationary phase pH effect at the time of using each of the various separation agents disclosed by Example 1, the comparative example 1, and the nonpatent literature 1. It is the radar chart which showed the result about the various evaluation items of Example 1 and Comparative Example 1 as a relative evaluation including the evaluation results of various separating agents disclosed in Non-Patent Document 1.
  • the chromatographic separation agent of the present invention comprises a porous substrate surface-modified with a silane functional group.
  • the silane functional group includes an aromatic ring modified with a diamine, and the aromatic ring is interposed between the porous substrate and the diamine.
  • the separation agent of the present invention further has an aromatic ring as another functional group. Since the aromatic ring exhibits a ⁇ interaction, it can be considered that the separation agent as a whole can advantageously exhibit a plurality of interactions in combination with the interaction exhibited by the diamine, and these provide excellent separation performance.
  • Such excellent separation performance includes a wide range of holding power, OH selectivity, CH 3 selectivity, configuration selectivity, regioisomer selectivity, molecular shape selectivity, anion exchange property, stationary phase surface pH effect, etc. It is.
  • the surface of the separating agent of the present invention typically exhibits hydrophilicity. Therefore, the separation agent of the present invention can be suitably used for HILIC (hydrophilic interaction chromatography), which is a chromatography using a hydrophilic stationary phase, and normal phase chromatography. It can be used.
  • HILIC hydrophilic interaction chromatography
  • the separating agent of the present invention is expected to be excellent in durability.
  • a separation agent having aminopropyl bonded thereto is known as a HILIC column.
  • the amino group dissolves the silica gel surface and deteriorates quickly.
  • the diamine becomes far from the porous substrate by interposing an aromatic ring between the porous substrate (for example, silica gel) and the diamine.
  • the movable range of the aromatic ring is small, the effect of avoiding the contact between the diamine and the porous substrate can be expected, thereby increasing the durability of the separating agent.
  • the porous substrate used in the present invention is not particularly limited as long as it can be surface-modified with a silane functional group, and is a variety of known porous substrates known as chromatographic separation agents (or stationary phases). be able to.
  • the form of the porous substrate is not particularly limited as long as it is porous, and may be in the form of particles or in the form of a bulk such as a monolith. That is, the porous substrate may be a porous particle or a porous bulk body.
  • the typical porous substrate is at least one selected from the group consisting of porous inorganic particles, porous inorganic bulk bodies, porous polymer particles, and porous polymer bulk bodies, preferably porous.
  • porous inorganic particles or porous inorganic bulk material particularly preferably porous inorganic particles.
  • the porous inorganic particles or the porous inorganic bulk material include silica gel, alumina silica gel, various ceramic particles having a hydroxyl group on the surface, and silica monolith, particularly preferably silica gel.
  • the porous polymer particles include cellulose particles, agarose particles, and other porous polymer particles having a hydroxyl group on the surface. But in the porous base material of the state by which the surface modification was carried out with the silane functional group, the hydroxyl group may remain
  • the porous substrate is surface-modified with a silane functional group.
  • a hydroxyl group for example, a silanol group in the case of silica gel
  • the silane functional group contains an aromatic ring modified with a diamine, and this aromatic ring is interposed between the porous substrate and the diamine. It is preferable that the meta position or the para position of the aromatic ring is modified with a diamine, and a mixture of a modification of the meta position of the aromatic ring and a modification of the para position of the aromatic ring may be used.
  • the diamine can contain any of primary amines, secondary amines and tertiary amines, but preferably contains secondary amines.
  • Amines are different in basicity among primary amines, secondary amines, and tertiary amines, but secondary amines have the highest basicity in aqueous solution and are particularly effective in separation performance such as selectivity and holding power. Contribute. Therefore, it is preferable to introduce two types of amines including secondary amines, that is, diamines, at the ends of the silane functional groups (that is, the positions farthest from the surface of the porous substrate).
  • the diamine is preferably an alkylene diamine having 2 to 17 carbon atoms, more preferably 2 to 13 carbon atoms, still more preferably 2 to 9 carbon atoms, particularly preferably 2 to 5 carbon atoms, and most preferably 2 to 2 carbon atoms. 3 alkylenediamine.
  • Particularly preferred diamines are — (CH 2 ) n NH (CH 2 ) m NH 2 , wherein n is 1 to 11, preferably 1 to 9, more preferably 1 to 5, particularly preferably 1 to 3, most preferably Is 1 and m is 1 to 6, preferably 1 to 4, particularly preferably 1 to 2, and most preferably 2.
  • the most preferred diamine is —CH 2 NH (CH 2 ) 2 NH 2 .
  • the aromatic ring may be any aromatic ring capable of exhibiting ⁇ interaction.
  • the aromatic ring include a benzene ring, a naphthalene ring, and an anthracene ring.
  • the most preferred aromatic ring is a benzene ring.
  • the number of aromatic rings contained in the silane functional group is 1.
  • the silane functional group includes a linking group comprising an alkylene group or oxyalkylene group having 1 to 6 carbon atoms between the silicon of the silane functional group and the aromatic ring.
  • alkylene group include a methylene group, a dimethylene group (ethylene group), a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, a propylene group, and an ethylethylene group.
  • Examples of the oxyalkylene group include an oxymethylene group, an oxydimethylene group (oxyethylene group), an oxytrimethylene group, an oxytetramethylene group, an oxypentamethylene group, an oxyhexamethylene group, and an oxypropylene group.
  • the number of carbon atoms of the alkylene group or oxyalkylene group is preferably 1 to 6, more preferably 1 to 3, and still more preferably 2.
  • a typical linking group is represented by — (CH 2 ) x —, and x is preferably 1 to 6, more preferably 1 to 3, and still more preferably 2. That is, a particularly preferred linking group is — (CH 2 ) 2 —.
  • silane functional group is: It is represented by
  • the separating agent of the present invention provides a silylating agent having a silane functional group as described above, and silylating the silylating agent and a porous substrate (typically a hydroxyl group present on the surface). Can be produced.
  • the silylation reaction may be performed according to known conditions, and is not particularly limited.
  • the chromatography column according to the present invention comprises a cylindrical column main body and the separation agent of the present invention packed or formed in the column main body.
  • the material which comprises a column main body is not specifically limited, For example, stainless steel, glass, etc. are mentioned.
  • the inner diameter and length of the column main body may be appropriately determined according to the application and are not particularly limited.
  • the separation agent may be filled or formed by any method.
  • the column main body may be packed with a particulate separation agent, or a bulk porous substrate such as a monolith (for example, a monolith type silica gel) may be formed in the column main body (for example, a capillary tube). That is, the chromatography column according to the present invention may be in the form of a monolithic capillary column.
  • the chromatographic separation method of the present invention includes a step of separating a plurality of substances using a chromatographic separating agent. That is, the separating agent of the present invention is used as a stationary phase for chromatography.
  • the mobile phase used for chromatography may be any of liquid, gas, and supercritical fluid, but liquid or supercritical fluid is preferable.
  • the separation method of the present invention may be any separation method using the principle of chromatography, in order to separate or concentrate compounds as a pretreatment for chemical analysis as well as various types of chromatography as chemical analysis methods.
  • the chromatography applicable to the separation method of the present invention may be any of liquid chromatography (for example, high performance liquid chromatography (HPLC)), gas chromatography, and supercritical chromatography. Critical fluid chromatography is preferred.
  • the separation mode of liquid chromatography is not particularly limited, and may be normal phase chromatography, HILIC (hydrophilic interaction chromatography), reverse phase chromatography or the like, but the separation agent of the present invention is used as a hydrophilic stationary phase. Normal phase chromatography or HILIC (a kind of normal phase chromatography) is particularly preferred because of its desirable properties.
  • Example 1 10 g of porous silica gel having an average particle size of 5 ⁇ m, an average pore size of 12 nm, and a specific surface area of 300 m 2 / g is dispersed in 50 mL of toluene. I let you. After cooling to room temperature, the silica gel after the reaction was filtered, washed, and dried under reduced pressure to obtain silica gel surface-modified with a silane functional group represented by the following general formula as a chromatographic separating agent.
  • Elemental analysis of the obtained separating agent was C: 11.69%, H: 1.60%, and N: 2.17%.
  • Comparative Example 1 10 g of porous silica gel having an average particle diameter of 5 ⁇ m, an average pore diameter of 12 nm, and a specific surface area of 300 m 2 / g is dispersed in 50 mL of toluene, and 11 g of bis (2-hydroxyethyl) -3-aminopropyltrimethoxysilane is added and refluxed. And allowed to react for 6 hours. After cooling to room temperature, the silica gel after the reaction was filtered, washed, and dried under reduced pressure to obtain silica gel surface-modified with a silane functional group represented by the following general formula as a chromatographic separating agent.
  • a silane functional group represented by the following general formula as a chromatographic separating agent.
  • Example 1 The separation agent obtained in Example 1 was packed in a stainless steel column body (column length: 100 mm, column inner diameter: 4.6 mm) to obtain a chromatography column.
  • a chromatography column For this chromatography column, the chromatographic performance in HILIC mode was evaluated by Non-Patent Document 1 (Yuusuke Kawachi, et al., “Chromatographic characterization of hydrophilic interaction liquid chromatography stationary phases: Hydrophilicity, charge effects, structural selectivity, and Separation efficiency ", Journal of Chromatography A. 1218 (2011) pp. 5903-5919, which is incorporated herein by reference). It was.
  • the same evaluation as in Example 1 was performed using a chromatography column produced in the same manner as described above using the separating agent obtained in Comparative Example 1.
  • the separation factor ⁇ was calculated as follows. First, the time of sample injection as 0, toluene contained in each sample (which is a compound that is not held in the separating agent) to the detection time of the t 0.
  • the detection time of the compound to be detected next to toluene (hereinafter referred to as the first compound) is t 1 and the compound to be detected next to the first compound (hereinafter referred to as the second compound). the detection time t 2 of.
  • toluene is a compound that is not retained by the separating agent in the HILIC mode, and therefore serves as a reference index for evaluating the degree of retention of the separating agent relative to other compounds (the same applies to samples 2 to 8 described later). Toluene is included for the reason).
  • 2′-deoxyuridine (2dU) and uridine (U) have very similar chemical structures to each other, and in the above chemical formula, the part circled is an —H group or an —OH group. The only difference is whether or not.
  • the retention force indicating the strength of hydrogen bonding can be evaluated from the retention time of U, and the difference in the presence or absence of OH groups depending on the value of ⁇ (U / 2dU) OH selectivity can be evaluated.
  • FIG. 1A shows the chromatogram of Sample 1 in Example 1
  • FIG. 1B shows the chromatogram of Sample 1 in Comparative Example 1.
  • Table 1 not only the retention force of U was extremely high but also the OH selectivity indicated by the value of ⁇ (U / 2dU) was extremely high by using the separating agent according to Example 1. It is understood that the reason why the holding power of U was large was that the separating agent of Example 1 had two types of amines and thus had strong hydrogen bonds. Moreover, it is considered that the separating agent of Example 1 contributed to the separation because it has a benzene ring in addition to the amine and has various interactions.
  • 5-methyluridine (5MU) and uridine (U) have chemical structures very similar to each other, and differ only in the presence or absence of —CH 3 group in the circled portion in the above chemical formula. . Therefore, by evaluating the separation performance for sample 2, CH 3 selectivity can be evaluated.
  • FIG. 2A The chromatogram of sample 2 in Example 1 is shown in FIG. 2A, while the chromatogram of sample 2 in Comparative Example 1 is shown in FIG. 2B.
  • Table 2 by using the separating agent according to Example 1, the CH 3 selectivity indicated by the value of ⁇ (U / 5MU) was high.
  • adenosine (A) and vidarabine (V) have very similar chemical structures, and differ only in the configuration of the circled portion in the above chemical formula. Therefore, by evaluating the separation performance with respect to the sample 3, the configuration selectivity can be evaluated.
  • FIG. 3A shows the chromatogram of Sample 3 in Example 1
  • FIG. 3B shows the chromatogram of Sample 3 in Comparative Example 1.
  • Table 3 by using the separating agent according to Example 1, the configuration selectivity shown by the value of ⁇ (V / A) was equivalent.
  • 3′-deoxyguanosine (3dG) and 2′-deoxyguanosine (2dG) have very similar chemical structures to each other, as can be seen from the comparison of the circled parts in the above chemical formula. Both are positional isomers. Therefore, regioisomer selectivity can be evaluated by evaluating the separation performance for sample 4.
  • FIG. 4A shows the chromatogram of Sample 4 in Example 1
  • FIG. 4B shows the chromatogram of Sample 4 in Comparative Example 1.
  • the regioisomer selectivity indicated by the value of ⁇ (2dG / 3dG) was equivalent by using the separating agent according to Example 1.
  • 4-nitrophenyl ⁇ -D-glucopyranoside (NP ⁇ Glu) and 4-nitrophenyl ⁇ -D-glucopyranoside (NP ⁇ Glu) have very similar chemical structures to each other, and are circled in the above chemical formula. The only difference is that the 4-nitrophenoxy group is bonded to the direction of the substituent of the other portion, that is, the axial position or the equatorial position. Therefore, the molecular shape selectivity can be evaluated by evaluating the separation performance with respect to the sample 5.
  • FIG. 5A shows the chromatogram of Sample 5 in Example 1
  • FIG. 5B shows the chromatogram of Sample 5 in Comparative Example 1.
  • the molecular shape selectivity indicated by the value of ⁇ (NP ⁇ Glu / NP ⁇ Glu) was equivalent by using the separating agent according to Example 1.
  • SPTS sodium p-toluenesulfonate
  • the chromatogram of sample 6 in Example 1 is shown in FIG. 6A, while the chromatogram of sample 6 in Comparative Example 1 is shown in FIG. 6B.
  • the anion exchange property indicated by the value of ⁇ (SPTS / U) was extremely high.
  • the secondary amine of the separating agent of Example 1 is generally considered to have the strongest basicity in an aqueous solution as compared with primary amines and tertiary amines (that is, NH 3 ⁇ (CH 3 ) 3 N ⁇ CH 3 NH 2 ⁇ (CH 3 ) 2 NH in the order of strong basicity), which is understood to have contributed to high anion exchangeability.
  • N, N, N-trimethylphenylammonium chloride is a highly anionic compound and has a tendency to be retained in the separating agent by cation exchange. Therefore, by evaluating the separation performance with respect to the sample 7, the cation exchange property can be evaluated.
  • FIG. 7A shows the chromatogram of Sample 7 in Example 1
  • FIG. 7B shows the chromatogram of Sample 7 in Comparative Example 1.
  • TMPAC which is a highly anionic compound
  • FIGS. 7A and 7B and Table 7 when the separating agent according to Example 1 is used, the retention time of TMPAC, which is a highly anionic compound, is substantially the same as the retention time of toluene as a reference index. It can be seen that TMPAC is not retained at all by the separating agent. That is, it can be seen that the separating agent of the present invention has no cation exchange property.
  • theophylline (Tp) and theobromine (Tb) differ in pKa due to the difference in the position of the —CH 3 group.
  • the basic stationary phase was eluted in the order of Tb to Tp, and the stationary phase surface pH effect was evaluated by the value of ⁇ (Tp / Tb).
  • FIG. 8A shows the chromatogram of Sample 8 in Example 1
  • FIG. 8B shows the chromatogram of Sample 1 in Comparative Example 1.
  • the separation performance indicated by the value of ⁇ (Tp / Tb) was extremely large by using the separation agent according to Example 1. That is, it can be seen that the separation agent of the present invention has extremely high separation performance as a basic stationary phase.
  • Non-Patent Document 1 the evaluation results are disclosed in Non-Patent Document 1, and the values (that is, Tpk, Tbk, and ⁇ (Tp / Tb)) in the commercially available separating agents listed below are the values of Example 1 and Comparative Example 1. 9 and Table 9 along with the values.
  • -ZIC-HILIC (3.5 ⁇ m, 5 ⁇ m, 150 ⁇ 4.6 mm ID) [Merck]
  • Nucleodur HILIC (3 ⁇ m, 150 ⁇ 4.6 mm ID) [NAGEL]
  • -Xbridge Amide (3.5 ⁇ m, 150 ⁇ 4.6 mm.
  • Tpk, Tbk, and ⁇ (Tp / Tb) shown in FIG. 9 are as follows.
  • -Tpk Theophylline (Tp) capacity factor
  • Tbk Theobromine (Tb) capacity factor- ⁇ (Tp / Tb): Separation factor when Tp is the second compound and Tb is the first compound
  • the high separation performance in Example 1 is considered to be due to the variety of interactions of the separation agent according to the present invention.
  • FIG. 10 shows a radar chart of the results of Example 1 and Comparative Example 1 for various items evaluated in the above (1) to (8).
  • standard which should be set to 1.00 in each item of the radar chart of FIG. 10 is the sample of the highest evaluation among the results of various separating agents disclosed in Example 1, Comparative Example 1, and Non-Patent Document 1.
  • FIG. 10 shows the results of the evaluation corresponding to the evaluation results and the relative evaluations for the evaluation results.
  • the various chromatographic performances of the separating agent prepared in Example 1 are greatly improved in comparison with Comparative Example 1 in many evaluation items, and are compared in other evaluation items. High performance comparable to Example 1 is demonstrated.
  • the separating agent of Example 1 is generally excellent in separating performance from a wide viewpoint, although it does not have cation exchange properties. It can be seen that In particular, since the separating agent of Example 1 has two types of amines and a benzene ring, it is considered that the hydrogen bonding k (U) has increased. Moreover, since the separating agent of Example 1 has a secondary amine, it is considered that anion exchange ⁇ (SPTS / U) is increased. Furthermore, since the separating agent of Example 1 has a benzene ring in addition to two types of amines, and thus exhibits a ⁇ interaction, it is considered that various interactions contributed to the improvement of the separation performance.
  • the separating agent of Comparative Example 1 has one kind of highly hydrophobic tertiary amine and a hydroxyl group, and the hydrogen bonding k (U) is smaller than that of Example 1.
  • the separating agent of Comparative Example 1 has a tertiary amine, it is considered that the anion exchange ⁇ (SPTS / U) is smaller because the basicity is smaller than that of the secondary amine of Example 1.
  • the OH selectivity ⁇ (U / 2dU) and stationary phase surface pH effect ⁇ (Tp / Tb) in the separating agent of Comparative Example 1 were significantly smaller than those of Example 1. Since the separating agent of Comparative Example 1 has only a hydroxyl group and a tertiary amine functional group, it is considered that a smaller number of types of interaction may have affected the separation as compared with Example 1.
  • the separation agent of the present invention is considered to be useful not only in the HILIC mode but also in chromatography using other separation modes such as a normal phase mode. .

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Abstract

L'invention concerne un agent de séparation pour chromatographie ayant une performance de séparation universellement exceptionnelle en termes de sélectivité, de force de rétention, et analogue. L'agent de séparation pour chromatographie comprend un substrat poreux qui est modifié en surface par un groupe fonctionnel silane comprenant un noyau aromatique modifié par une diamine, le noyau aromatique étant intercalé entre le substrat poreux et la diamine.
PCT/JP2016/087973 2015-12-25 2016-12-20 Agent de séparation pour chromatographie, colonne chromatographique, et procédé de séparation par chromatographie WO2017110819A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07103955A (ja) * 1993-10-05 1995-04-21 Daiso Co Ltd クロマトグラフ充填剤
JP2006507122A (ja) * 2002-11-22 2006-03-02 カーネギー−メロン　ユニバーシティ 生体分子の可逆的捕捉のための組成物と方法
WO2013176215A1 (fr) * 2012-05-23 2013-11-28 株式会社ダイセル Agent de séparation
WO2014087937A1 (fr) * 2012-12-06 2014-06-12 株式会社ダイセル Agent de séparation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07103955A (ja) * 1993-10-05 1995-04-21 Daiso Co Ltd クロマトグラフ充填剤
JP2006507122A (ja) * 2002-11-22 2006-03-02 カーネギー−メロン　ユニバーシティ 生体分子の可逆的捕捉のための組成物と方法
WO2013176215A1 (fr) * 2012-05-23 2013-11-28 株式会社ダイセル Agent de séparation
WO2014087937A1 (fr) * 2012-12-06 2014-06-12 株式会社ダイセル Agent de séparation

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