CN114146696A - Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology - Google Patents
Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology Download PDFInfo
- Publication number
- CN114146696A CN114146696A CN202111340994.8A CN202111340994A CN114146696A CN 114146696 A CN114146696 A CN 114146696A CN 202111340994 A CN202111340994 A CN 202111340994A CN 114146696 A CN114146696 A CN 114146696A
- Authority
- CN
- China
- Prior art keywords
- chiral
- organic framework
- sio
- composite material
- metal organic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000463 material Substances 0.000 title claims abstract description 122
- 239000012924 metal-organic framework composite Substances 0.000 title claims abstract description 98
- 230000005526 G1 to G0 transition Effects 0.000 title claims abstract description 76
- 238000012986 modification Methods 0.000 title claims abstract description 68
- 238000005516 engineering process Methods 0.000 title claims abstract description 54
- 238000003821 enantio-separation Methods 0.000 title description 3
- 239000012621 metal-organic framework Substances 0.000 claims abstract description 79
- 239000003446 ligand Substances 0.000 claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 44
- 239000002253 acid Substances 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 230000003637 steroidlike Effects 0.000 claims abstract description 8
- 238000004943 liquid phase epitaxy Methods 0.000 claims abstract description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 113
- 229910052681 coesite Inorganic materials 0.000 claims description 96
- 229910052906 cristobalite Inorganic materials 0.000 claims description 96
- 229910052682 stishovite Inorganic materials 0.000 claims description 96
- 229910052905 tridymite Inorganic materials 0.000 claims description 96
- 239000000377 silicon dioxide Substances 0.000 claims description 66
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
- 238000004811 liquid chromatography Methods 0.000 claims description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 238000001291 vacuum drying Methods 0.000 claims description 32
- 238000003756 stirring Methods 0.000 claims description 29
- 229910052751 metal Inorganic materials 0.000 claims description 26
- 239000002184 metal Substances 0.000 claims description 26
- 238000005406 washing Methods 0.000 claims description 26
- 239000006185 dispersion Substances 0.000 claims description 22
- 239000013110 organic ligand Substances 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000001035 drying Methods 0.000 claims description 16
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 14
- 229940014800 succinic anhydride Drugs 0.000 claims description 14
- 238000005576 amination reaction Methods 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 239000007822 coupling agent Substances 0.000 claims description 10
- 230000003213 activating effect Effects 0.000 claims description 9
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims description 8
- 239000003223 protective agent Substances 0.000 claims description 8
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 7
- 229960000991 ketoprofen Drugs 0.000 claims description 7
- 239000012450 pharmaceutical intermediate Substances 0.000 claims description 7
- LSPHULWDVZXLIL-LDWIPMOCSA-N (?)-Camphoric acid Chemical compound CC1(C)[C@@H](C(O)=O)CC[C@@]1(C)C(O)=O LSPHULWDVZXLIL-LDWIPMOCSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- -1 phosphonium bromide hexafluorophosphate salt Chemical compound 0.000 claims description 5
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 3
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 3
- CDRQOYRPWJULJN-UHFFFAOYSA-N 1-naphthalen-1-ylethanol Chemical compound C1=CC=C2C(C(O)C)=CC=CC2=C1 CDRQOYRPWJULJN-UHFFFAOYSA-N 0.000 claims description 3
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- 150000008575 L-amino acids Chemical class 0.000 claims description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 3
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 3
- 229960001419 fenoprofen Drugs 0.000 claims description 3
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 3
- 229960002390 flurbiprofen Drugs 0.000 claims description 3
- 229960001680 ibuprofen Drugs 0.000 claims description 3
- 229960002510 mandelic acid Drugs 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 14
- 238000000926 separation method Methods 0.000 abstract description 10
- 230000008901 benefit Effects 0.000 abstract description 9
- 239000011148 porous material Substances 0.000 abstract description 8
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052710 silicon Inorganic materials 0.000 abstract description 4
- 239000010703 silicon Substances 0.000 abstract description 4
- 230000007547 defect Effects 0.000 abstract description 3
- 238000001338 self-assembly Methods 0.000 abstract description 3
- 150000007513 acids Chemical class 0.000 abstract description 2
- 238000013375 chromatographic separation Methods 0.000 abstract description 2
- 238000011065 in-situ storage Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002245 particle Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- GPNNOCMCNFXRAO-UHFFFAOYSA-N 2-aminoterephthalic acid Chemical compound NC1=CC(C(O)=O)=CC=C1C(O)=O GPNNOCMCNFXRAO-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 238000006473 carboxylation reaction Methods 0.000 description 7
- 238000000527 sonication Methods 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 239000007795 chemical reaction product Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000004140 cleaning Methods 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 4
- AWMVMTVKBNGEAK-QMMMGPOBSA-N (R)-styrene oxide Chemical compound C1O[C@@H]1C1=CC=CC=C1 AWMVMTVKBNGEAK-QMMMGPOBSA-N 0.000 description 4
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- YPGCWEMNNLXISK-ZETCQYMHSA-N (S)-hydratropic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC=C1 YPGCWEMNNLXISK-ZETCQYMHSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 3
- 229910007932 ZrCl4 Inorganic materials 0.000 description 3
- YPGCWEMNNLXISK-UHFFFAOYSA-N alpha-phenylpropionic acid Natural products OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000011258 core-shell material Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 239000013384 organic framework Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 229910052726 zirconium Inorganic materials 0.000 description 3
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 3
- NLMMSZKFLSMODY-UHFFFAOYSA-N 3-amino-6-phenylphthalic acid Chemical compound NC1=C(C(=C(C=C1)C1=CC=CC=C1)C(=O)O)C(=O)O NLMMSZKFLSMODY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910021556 Chromium(III) chloride Inorganic materials 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- JLDSOYXADOWAKB-UHFFFAOYSA-N aluminium nitrate Chemical compound [Al+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O JLDSOYXADOWAKB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000021523 carboxylation Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000005557 chiral recognition Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000011636 chromium(III) chloride Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002715 modification method Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- FYEKGZUXGKAJJQ-UHFFFAOYSA-N 3-amino-4-(4-carboxyphenyl)benzoic acid Chemical compound NC1=CC(C(O)=O)=CC=C1C1=CC=C(C(O)=O)C=C1 FYEKGZUXGKAJJQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 239000013206 MIL-53 Substances 0.000 description 1
- VENYPRKAFCOCDN-UHFFFAOYSA-J NC1=C(C(=CC=C1)C(=O)[O-])C(=O)[O-].[Zr+4].NC1=C(C(=CC=C1)C(=O)[O-])C(=O)[O-] Chemical class NC1=C(C(=CC=C1)C(=O)[O-])C(=O)[O-].[Zr+4].NC1=C(C(=CC=C1)C(=O)[O-])C(=O)[O-] VENYPRKAFCOCDN-UHFFFAOYSA-J 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000010888 cage effect Methods 0.000 description 1
- 230000003047 cage effect Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- B01J20/29—Chiral phases
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3833—Chiral chromatography
Landscapes
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention relates to a preparation method and application of a metal organic framework composite material chiral chromatographic stationary phase based on a post-modification technology. The invention takes silicon spheres as a separation medium, adopts a liquid phase epitaxy method to generate a metal organic framework material by in-situ self-assembly on the surfaces of the silicon spheres, and utilizes a post-modification technology to introduce chiral ligands to form the metal organic framework composite material chiral stationary phase. On the basis, the material is used for chromatographic separation of the racemes of arylpropionic acids in aromatic and non-steroidal medicines in the medicine intermediate. The preparation method provided by the invention is simple and convenient to operate, the raw materials are cheap and easy to obtain, the obtained material has the advantages of large specific surface area and adjustable pore diameter of the MOFs material, the defects of poor dispersity and poor stability of the conventional chiral MOFs chromatographic stationary phase are overcome, the selective recognition capability of the chiral chromatographic stationary phase can be improved, the application range of the chiral MOFs as a separation medium is expanded, and the preparation method has a wide application prospect.
Description
Technical Field
The invention belongs to the field of chiral chromatographic resolution, relates to a metal organic framework composite material chiral chromatographic stationary phase based on a post-modification technology, and particularly relates to a metal organic framework composite material chiral chromatographic stationary phase based on the post-modification technology, and a preparation method and application thereof.
Background
Many macromolecular substances in a life system, such as proteins and nucleic acids, and receptors on the surfaces of target cells and enzymes generally have chirality, and after a chiral drug enters the life system, the physiological activity of the chiral drug mainly depends on chiral matching with the target cells and a molecular recognition mechanism. This puts high demands on the optical purity of chiral drugs, so chiral resolution techniques are of great importance in the pharmaceutical field. In the chiral resolution technology, compared with other resolution technologies, the chromatographic resolution method has the advantages of simple and convenient operation, good selectivity, small dosage and short experimental period, and can meet the requirements of separation and determination of various enantiomers. Therefore, the method has great application potential in chiral separation.
The chromatographic chiral separation mainly depends on the principle of three-point interaction, one configuration can form a stable state with the chiral stationary phase through three-point interaction between a pair of enantiomers and the chiral stationary phase, and the other configuration can only form an unstable state through two-point interaction, so that the aim of chiral separation is fulfilled. This therefore places higher demands on the chiral stationary phase. With the development of new chiral resolution materials, metal organic framework materials have received much attention due to their excellent properties.
The metal organic framework material has the advantages of large specific surface area, high porosity, adjustable pore diameter, strong stability and the like, and is suitable for being used as a chromatographic stationary phase material. In addition, the metal organic framework can introduce a chiral center through a direct synthesis method, meets the requirements of stereochemical sites, simultaneously has interaction forms such as pi-pi stacking interaction, coordination and chelation of metal ions, hydrophobic interaction, cage effect and the like, and provides various intermolecular interaction forces to enhance chiral resolution performance after meeting chiral recognition sites. However, the direct synthesis method uses a chiral compound as an organic framework to be in coordination connection with metal ions, and can obtain higher chiral ligand density, but because chiral molecules are in an asymmetric structure, the MOFs crystal formed by the method has non-uniform morphology and poor chromatographic stability, and the application of the MOFs crystal in chiral chromatographic resolution is limited.
Disclosure of Invention
The invention aims to solve the technical problem of the prior art and provides a metal organic framework composite material chiral chromatographic stationary phase based on a post-modification technology and a preparation method thereof. The metal organic framework composite material chiral chromatographic stationary phase prepared by the method overcomes the defects of poor dispersity and poor stability of the existing chiral MOFs chromatographic stationary phase, and chiral sites are introduced by utilizing a post-modification technology, so that the chiral MOFs can be designed rationally according to requirements while the chiral recognition effect is met, and the chromatographic performance of the MOFs chromatographic stationary phase is improved.
To this end, the invention provides, in a first aspect, a chiral liquid chromatography stationary phase of a metal-organic framework composite material based on a post-modification technology, the metal-organic framework composite material based on the post-modification technology comprising SiO2A core, and coated in SiO2The MOFs layer is coated on the outer surface of the core, wherein the MOFs layer is coated on the SiO by a liquid phase epitaxy method2And (3) bonding a chiral ligand on the MOFs layer by utilizing a post-modification technology.
In the present invention, the SiO2Has a grain size of 5 μm, and the material constituting the MOFs layer comprises UiO-66-NH2、UiO-67-NH2、MIL-53-NH2And MIL-101-NH2One or more of the above; and/or the thickness of the MOFs layer is 10-1000nm, preferably 100-500 nm.
In some embodiments of the invention, the chiral ligand used for post-modification comprises one or more of L-tartaric acid, L-amino acids, D-camphoric acid, R-styrene oxide, and S-2-phenylpropionic acid.
The second aspect of the present invention provides a method for preparing the chiral liquid chromatography stationary phase of the metal organic framework composite material based on the post-modification technology, which comprises:
step A, towards SiO2Adding coupling agent into the dispersion, stirring, reacting, washing, centrifugally separating and drying to obtain aminated SiO2；
Step B, amination SiO2Adding the dispersion into succinic anhydride solution, stirring, reacting, washing, and drying to obtain carboxylChemical SiO2；
Step C, carboxylating SiO containing soluble metal salt2Mixing the dispersion liquid with the organic ligand solution, stirring, reacting, washing, activating and drying to obtain the metal-organic framework composite material;
and D, adding the metal organic framework composite material solution into the chiral ligand solution, stirring, reacting, washing and drying to obtain the chiral chromatographic stationary phase of the metal organic framework composite material based on the post-modification technology.
In the invention, in the step D, the chiral ligand solution is prepared by dissolving the chiral ligand in an organic solvent; the concentration of the chiral ligand solution is 1-40 mmol/L; the chiral ligand comprises one or more of L-tartaric acid, D-camphoric acid, R-epoxyphenylethane and S-2-phenylpropionic acid; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
According to the invention, in step D, optionally adding a carboxyl protecting agent to the chiral ligand solution before mixing the chiral ligand solution with the metal organic framework material solution; preferably, the molar ratio of the chiral ligand to the carboxyl-containing protective agent is 1 (0-4); and/or, the carboxy protecting agent includes, but is not limited to, a trispyrrolidinyl phosphonium bromide hexafluorophosphate salt.
In some embodiments of the present invention, in step D, the metal-organic framework composite solution is prepared by dissolving a metal-organic framework composite in an organic solvent; the concentration of the metal organic framework composite material solution is 1-20 mg/L; preferably, the concentration of the metal organic framework composite material solution is 8-15 mg/L; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
According to the invention, in step D, optionally adding a catalyst to the metal-organic framework composite solution; the mass ratio of the metal organic framework composite material to the catalyst is 1: (0-3); preferably, the catalyst includes, but is not limited to, 4-dimethylaminopyridine.
According to the invention, in the step D, the mass ratio of the chiral ligand to the chiral metal-organic framework material is 1 (0.5-5).
In the invention, in the step D, the stirring speed of the reaction of the metal-organic framework composite material and the chiral ligand solution is 100-800 rpm.
In some embodiments of the invention, in step D, the temperature of the reaction is room temperature.
In other embodiments of the present invention, in step D, the reaction time is 12 to 168 hours, preferably 12 to 120 hours.
In some particularly preferred embodiments of the invention, in step D, the mixture is washed with ethanol, dried under vacuum at 80 ℃, activated in dichloromethane for 6 to 96 hours, and finally dried under vacuum at 100 ℃.
The third aspect of the present invention provides the use of the chiral liquid chromatography stationary phase of the metal-organic framework composite material based on the post-modification technology according to the first aspect of the present invention, or the chiral liquid chromatography stationary phase of the metal-organic framework composite material based on the post-modification technology according to the method according to the second aspect of the present invention, in the chromatographic resolution of aromatic racemates used as pharmaceutical intermediates and arylpropionic acid racemates used as non-steroidal drugs.
In some embodiments of the present invention, the aromatic racemate used as a pharmaceutical intermediate comprises one or more of 1-phenylethanol, methylbenzylamine, mandelic acid and 1- (1-naphthyl) ethanol.
In other embodiments of the present invention, the racemate of arylpropionic acids used as the non-steroidal drug includes one or more of ibuprofen, ketoprofen, naproxen, fenoprofen and flurbiprofen.
Compared with the prior art, the invention has the following advantages:
(1) the invention adopts an in-situ synthesis mode, and has the characteristics of simple synthesis method, low cost, easy realization of industrialization and the like.
(2) The liquid chromatographic column of the metal organic framework composite material obtained by the invention combines the dual separation advantages of MOFs and the traditional liquid chromatographic column, and has the advantages of good permeability, capability of rapid separation and the like.
(3) The chiral liquid chromatography stationary phase of the metal organic framework composite material based on the post-modification technology overcomes the defects of poor dispersity and poor chromatographic stability of the existing chiral MOFs chromatography stationary phase, can design and construct chiral MOFs aiming at different enantiomers, is favorable for improving the selection specificity and the selection recognition capability, has very high chromatographic resolution, expands the application range of the chiral MOFs as a separation medium, and is favorable for large-scale popularization.
Drawings
The invention is described in further detail below with reference to the attached drawing figures:
FIG. 1 shows chiral MOFs @ SiO in example 12XRD contrast pattern of (a).
FIG. 2 shows MOFs @ SiO in example 12FT-IR diagram of (1).
FIG. 3 shows MOFs @ SiO in example 12SEM picture of (1); wherein (a) SiO2-COOH；(b)MOFs@SiO2(ii) a (c) Chiral MOFs @ SiO2。
FIG. 4 is the MOFs @ SiO in example 12N of (A)2Adsorption and desorption isotherm diagram; wherein, (a) MOFs @ SiO2(ii) a (b) Chiral MOFs @ SiO2。
FIG. 5 is a liquid chromatogram of the chiral stationary phase for detecting ketoprofen in example 1.
FIG. 6 is a liquid chromatogram of chiral stationary phase detection of methylbenzylamine in example 2.
Detailed Description
In order that the invention may be readily understood, a more particular description thereof will be rendered by reference to the appended drawings. However, before the invention is described in detail, it is to be understood that this invention is not limited to particular embodiments described. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.
Unless otherwise defined, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described.
Term (I)
The term "stationary phase" as used herein means a phase which is stationary during chromatographic separation and which is retained by the sample. The phase of column chromatography or plate chromatography that is both separating and immobile.
The term "SiO" according to the invention2@ MOFs "means solid-phase particles of core-shell structure, i.e.in" SiO2The solid-phase particles with the core-shell structure are formed by coating a layer of MOFs layer on the outer layer of the particle core, wherein the symbol '@' refers to the core-shell structure.
SiO as core in the invention2Has a particle diameter of 5 μm, the SiO2And silicon spheres may be used interchangeably.
The term "optional" as used herein means that optional ingredients may or may not be added.
Embodiments II
As mentioned previously, existing methods for preparing MOFs chromatographic stationary phases have mainly focused on the formation of chiral MOFs using chiral molecules as organic ligands and binding to metal sites. However, as chiral molecules are asymmetric structures, the formed MOFs crystal has non-uniform morphology and poor chromatographic stability, and the application of the MOFs crystal in chiral chromatographic resolution is limited. In view of this, the present inventors have conducted extensive studies on MOFs-based chromatographic stationary phases and separation effects thereof.
The inventor researches and discovers that the chiral post-modification method is to modify chiral molecules on the surface of the MOFs on an achiral MOFs framework so as to introduce a chiral function, the method keeps the crystallinity of the MOFs and well solves the problem of poor stability. The method has another advantage that chiral sites can be rationally designed according to the needs of chiral resolution, so that the needs of chiral resolution under different conditions are met. In addition, the MOFs material and the silica material with excellent chromatographic performance form a shell-core structure by utilizing a self-assembly method, and the resolution performance and the fluid performance of the MOFs as a chromatographic stationary phase can be further improved. Therefore, the metal organic framework composite material chiral chromatographic stationary phase based on the post-modification technology has good application prospect in chiral chromatographic resolution.
Therefore, the invention relates to a chiral liquid chromatography stationary phase of a metal organic framework composite material based on a post-modification technology, and the metal organic framework composite material based on the post-modification technology comprises SiO2A core, and coated in SiO2The MOFs layer is coated on the outer surface of the core, wherein the MOFs layer is coated on the SiO by a liquid phase epitaxy method2And (3) bonding a chiral ligand on the MOFs layer by utilizing a post-modification technology.
The metal organic framework composite material comprises SiO2A core, and coated in SiO2MOFs layer on the outer surface of the core, in the invention, SiO is used2@ MOFs stands for, whereas metal-organic framework composites based on post-modification techniques can be understood as being based on metal-organic framework composites (SiO)2@ MOFs) by bonding a chiral ligand to the MOFs layer, it can be expressed as SiO based on post-modification technology2@ MOFs, this being understood further as a composite material with a metal-organic framework based on post-modification technology (SiO based on post-modification technology)2@ MOFs) as the stationary phase of chiral liquid chromatography, or a metal organic framework composite material based on post-modification technology (SiO based on post-modification technology)2@ MOFs), also referred to herein as SiO based post-modification techniques2@ MOFs chiral liquid chromatography stationary phase; therefore, it is easy to understand that in the mention of metal organic framework composite materials based on post-modification technology (SiO based on post-modification technology)2@ MOFs) is SiO as a component2The chiral liquid chromatography stationary phase of @ MOFs, i.e., SiO based on post-modification techniques2@ MOFs chiral liquid chromatography stationary phase.
The metal organic framework composite material chiral liquid chromatography fixed phase based on post-modification technology:
the SiO2Has a particle diameter of 5 μm.
The thickness of the MOFs layer is 10-2000nm, preferably 100-1000nm, and more preferably 100-500 nm. Preferably, the material constituting the MOFs layer comprises UiO-66-NH2、UiO-67-NH2、MIL-53-NH2And MIL-101-NH2One or more of them.
"UiO-66-NH" as described in the present invention2"(Zirconium aminobenzenedicarboxylates MOF) is a Zirconium-containing MOF material having a unit molecular formula of C48H34N6O32Zr6The molecular weight is 1754.15, the coordination metal is Zr, the ligand is 2-amino-p-benzoic acid, and the molecular structural formula is shown as formula (1).
In the present invention, "UiO-67-NH2"(Zirconium amidinophenyldicarboylate MOF) is a Zirconium-containing MOF material having a unit molecular formula of C84H58N6O32Zr6The molecular weight is 2210.58, the coordination metal is Zr, the ligand is 2-amino-4, 4' -biphenyl dicarboxylic acid, and the molecular structural formula is shown as formula (2).
"NH" as defined in the invention2MIL-53(Al) "(aluminum aminobenzinedicarboxylates MOF) is an aluminum-containing MOF material having a unit molecular formula of C8H5NO5The unit molecular weight of Al is 222.11, the coordination metal is Al, the ligand is 2-amino terephthalic acid, and the molecular structural formula is shown as a formula (3).
The "MIL-101-NH2(Al)' Unit molecular formula is C24H15N3O13Al9The molecular weight is 796.23, the coordination metal is Al, the ligand is 2-amino terephthalic acid, and the molecular structural formula is shown as a formula (4).
The specific surface area of the chiral liquid chromatography stationary phase of the metal organic framework composite material based on the post-modification technology is 540-2·g-1(ii) a For example, in some examples, the chiral liquid chromatography stationary phase of the metal-organic framework composite material based on the post-modification technology has a specific surface area of 700m2·g-1、730m2·g-1、1100m2·g-1、1900m2·g-1。
The average pore diameter of the chiral liquid chromatography stationary phase of the metal organic framework composite material based on the post-modification technology is
Specifically comprises
In some embodiments of the invention, the chiral ligand used for post-modification comprises one or more of L-tartaric acid, L-amino acids, D-camphoric acid, R-styrene oxide, and S-2-phenylpropionic acid.
The method for preparing the chiral liquid chromatography stationary phase of the metal organic framework composite material based on the post-modification technology comprises the following steps:
and 4, adding the metal organic framework composite material solution into the chiral ligand solution, stirring, reacting, washing and drying to obtain the chiral chromatographic stationary phase of the metal organic framework composite material based on the post-modification technology.
As described above, the technical problem to be solved by the present invention is to provide a post-modification technique based metal-organic framework composite chiral chromatography stationary phase and a preparation method thereof, and the post-modification technique based metal-organic framework composite material used as the chiral liquid chromatography stationary phase prepared by the method comprises SiO2A core, and coated in SiO2The MOFs layer is coated on the outer surface of the core, wherein the MOFs layer is coated on the SiO by a liquid phase epitaxy method2The core outer surface is bonded with chiral ligand on MOFs layer by post-modification technology, i.e. metal organic framework composite material (SiO)2@ MOFs) on the MOFs layer to obtain the metal organic framework composite material chiral chromatographic stationary phase based on the post-modification technology. The preparation of the metal organic framework composite material (SiO)2@ MOFs) the specific operations of steps 1-3 may refer to chinese patent CN 202010720631.6.
It will be appreciated by those skilled in the art that when it is desired to prepare SiO as a stationary phase for liquid chromatography based on a metal organic framework composite2When the MOFs layer on the outer surface of the core is a UiO material containing Zr, an acid solution is required to be added in the step 3.
When the post-modified ligands to be prepared are (S) -2-phenylpropionic acid, L-tartaric acid and (D) -camphoric acid, a carboxyl protecting agent needs to be added into the chiral ligand solution in the step 4.
When the post-modification ligands to be prepared are (S) -2-phenylpropionic acid, L-tartaric acid and (D) -camphoric acid, in the step 4, a catalyst needs to be added into the metal-organic framework composite material solution.
(1) the SiO2The dispersion consists of SiO2Dispersing in absolute ethyl alcohol to obtain the product; in the SiO2In a dispersion, SiO2The content of (b) is 0.03-0.05 g/mL.
(2) The SiO2The mass-to-volume ratio of the coupling agent to the coupling agent is 0.1 to 2g/mL, preferably 1 to 2 g/mL.
(3) The coupling agent includes, but is not limited to, an amino silylating agent, which is preferably 3-aminopropyltriethoxysilane.
(4) The reaction temperature is 50-90 ℃, preferably 70-90 ℃, and further preferably 70 ℃; the reaction time is 12 to 48 hours, preferably 24 to 48 hours, and more preferably 24 hours.
(5) Washing with absolute ethanol at least once, preferably 3 times; the product was centrifuged and dried in a vacuum oven at 70 ℃ for 8 h.
In some specific embodiments, in step 1, SiO with a particle size of 5 μm2Adding into anhydrous ethanol, stirring for 60min to obtain SiO2A dispersion liquid; adding 3-aminopropyltriethoxysilane as coupling agent, heating to 50-90 deg.C, preferably 70-90 deg.C, more preferably 70 deg.C, stirring for reaction for 12-48 hr, preferably 24-48 hr, more preferably 24 hr; and after the reaction is finished, washing the reaction product with absolute ethyl alcohol for three times, centrifuging the reaction product, and putting the product into a vacuum drying oven at the temperature of 60-70 ℃ for vacuum drying for 8 hours to obtain dry aminated SiO2 particles.
In the step 2, amination of SiO is carried out by succinic anhydride2By carboxylation of SiO2Preparation of carboxylated SiO2The specific reaction conditions are as follows:
(1) the succinic anhydride solution is prepared by dissolving succinic anhydride in DMF; the content of succinic anhydride in the succinic anhydride solution is 0.05 to 0.5g/mL, preferably 0.10 to 0.5g/mL, and more preferably 0.10 g/mL.
(2) The aminated SiO2The dispersion consists of aminated SiO2Dispersing in DMF to obtain; in the aminated SiO2In dispersion, amination of SiO2The content of (B) is 0.05-0.2g/mL, preferably 0.05-0.1 g/mL.
(3) The mass ratio of the aminated SiO2 to succinic anhydride is 1 (1-5), preferably 1 (2-5), and more preferably 1: 2.
(4) The temperature of the reaction is room temperature; the reaction time is 12 to 48 hours, preferably 24 to 48 hours, and more preferably 24 hours.
In some specific embodiments, in step 2, succinic anhydride is added into DMF, and stirred to dissolve after nitrogen blowing, so as to prepare a succinic anhydride solution; amination of SiO2Ultrasonically dispersing in DMF to prepare aminated SiO2 dispersion; amination of SiO2Dropwise adding the dispersion into a succinic anhydride solution, and stirring and reacting for 12-48 hours, preferably 24-48 hours, and further preferably 24 hours at room temperature; washing the mixture for three times by using DMF (dimethyl formamide) after the reaction is finished, and washing the mixture for three times by using absolute ethyl alcohol; centrifuging, placing the product in a vacuum drying oven at 60-70 deg.C, vacuum drying for 8 hr to obtain dried carboxylated SiO2And (3) granules.
In step 3, by carboxylation of SiO with soluble metal salts2The dispersion liquid and the organic ligand solution are mixed and reacted to prepare the liquid chromatogram fixed phase based on the metal organic framework composite material, and the specific reaction conditions are as follows:
(1) the soluble metal salt solution is prepared by dissolving soluble metal salt in DMF, and the concentration of the soluble metal salt solution is 0.01-0.05 mmol/mL; the soluble metal salt comprises ZrCl4、AlCl3·6H2O、Al(NO3)3·H2O、FeCl3·6H2O and CrCl3One or more of them.
(2) The carboxylated SiO containing soluble metal salt2The dispersion consisting of carboxylated SiO2Dispersed in a soluble metal salt solution, said carboxylated SiO2The mass ratio of the soluble metal salt to the soluble metal salt is 1 (0.2-2), preferably 1: 2.
(3) The organic ligand solution is prepared by dissolving an organic ligand in DMF, and the concentration of the organic ligand solution is 0.01-0.05 mmol/mL; the organic ligand comprises aminoterephthalic acid and/or aminobiphenyl dicarboxylic acid.
(4) The acid solution is added in a dropwise manner; carboxylic acids containing soluble metal saltsBased SiO2The volume ratio of the mixed solution of the dispersion liquid and the organic ligand solution to the acid solution is 1 (0-6); preferably, the addition amount of the acid solution is 1-10 mL; the acid solution comprises one or more of hydrochloric acid, acetic acid, sulfuric acid, nitric acid and oxalic acid, and is preferably acetic acid or hydrochloric acid.
(5) The carboxylated SiO2The mass ratio of the organic ligand to the organic ligand is 1 (0.2-2), preferably 1: 2.
(6) The stirring rotating speed is 100-800 pm; the temperature of the reaction is 100-140 ℃; the reaction time is 6-72 hours
(7) Washing with N, N-dimethylformamide and dichloromethane sequentially, vacuum drying at 40-60 deg.C, activating in dichloromethane solution for 6-72 hr, and vacuum drying at 40-60 deg.C.
In the present invention, the acid solution is used as it is in a commercially available concentration.
In some embodiments, in step 3, the soluble metal salt is ultrasonically dissolved in DMF and carboxylated SiO is added2To prepare carboxylated SiO containing soluble metal salt2A dispersion liquid; ultrasonically dissolving an organic ligand amino terephthalic acid in DMF to prepare an organic ligand solution; adding an organic ligand solution to carboxylated SiO containing a soluble metal salt2And (3) forming a suspension in the dispersion, heating to the temperature of 100-140 ℃, stirring for reacting for 6-72 hours, washing with N, N-dimethylformamide and dichloromethane in sequence, drying at 40 ℃ in vacuum, activating in a dichloromethane solution for 6-72 hours, and finally drying at 40 ℃ in vacuum to obtain the metal organic framework composite material.
In the step 4, the chiral ligand solution reacts with amino groups on the framework in the metal organic framework composite material to prepare the metal organic framework composite material chiral chromatographic stationary phase, and the specific reaction conditions are as follows:
(1) the chiral ligand solution is prepared by dissolving chiral ligands in an organic solvent; the concentration of the chiral ligand solution is 1-40 mmol/L; the chiral ligand comprises one or more of L-tartaric acid, D-camphoric acid, R-epoxyphenylethane and S-2-phenylpropionic acid; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
(2) The metal organic framework composite material solution is prepared by dissolving a metal organic framework composite material in an organic solvent; the concentration of the metal organic framework composite material solution is 1-20 mg/L; preferably, the concentration of the metal organic framework composite material solution is 8-15 mg/L; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
(3) The mass ratio of the chiral ligand to the chiral metal organic framework material is 1: (0.5-5). The stirring speed is 100-800 rpm; and/or the temperature of the reaction is room temperature; and/or the reaction time is 12 to 168 hours, preferably 12 to 120 hours.
(4) Washing with ethanol, vacuum drying at 80 deg.C, activating in dichloromethane solution for 6-96 hr, and vacuum drying at 100 deg.C.
In some embodiments, in step 4(1), the chiral ligand is added to the organic reagent and ultrasonically dissolved to prepare a chiral ligand solution; adding a carboxyl protective agent into the solution; ultrasonically dispersing the metal organic framework composite material in the same organic reagent to prepare a metal organic framework composite material solution; adding a catalyst into the solution; mixing the chiral ligand solution and the metal organic framework composite material solution, and stirring to react for 12-168 hours, preferably 12-120 hours, at room temperature; washing the reaction product with absolute ethyl alcohol for three times after the reaction is finished; centrifuging, and vacuum drying the product in a vacuum drying oven at 80 deg.C for 8 hr; activating the dried product in dichloromethane solution for 6-96 hours, and finally drying in vacuum at 100 ℃ for 8 hours to obtain the metal organic framework composite material chiral chromatographic stationary phase.
The metal organic framework composite material chiral liquid chromatography stationary phase based on the post-modification technology comprises SiO2A core, and coated in SiO2MOFs layer on the outer surface of the core and chiral ligand bonded on the organic framework. The SiO2The particle size of the chiral ligand is 5 mu m, the thickness of the MOFs layer is 1-100nm, preferably 1-10nm, and the grafting rate of the chiral ligand is 10-50%.
In the third aspect of the present invention, the use of the chiral liquid chromatography stationary phase of metal organic framework composite material based on post-modification technology according to the first aspect of the present invention or the chiral liquid chromatography stationary phase of metal organic framework composite material based on post-modification technology prepared by the method according to the second aspect of the present invention in the chromatographic resolution of aromatic racemates used as drug intermediates and arylpropionic acid racemates used as non-steroidal drugs, this may be understood as a method for chromatographic resolution of aromatic racemates for use as pharmaceutical intermediates and arylpropionic acid racemates for use as non-steroidal drugs using the metal organic framework composite chiral liquid chromatography stationary phase based on the post-modification technique according to the first aspect of the present invention or the metal organic framework composite chiral liquid chromatography stationary phase based on the post-modification technique prepared by the method according to the second aspect of the present invention.
In some embodiments of the present invention, the aromatic racemate used as a pharmaceutical intermediate comprises one or more of 1-phenylethanol, methylbenzylamine, mandelic acid and 1- (1-naphthyl) ethanol.
In some embodiments of the invention, the racemate of the arylpropionic acid used as the non-steroidal drug comprises one or more of ibuprofen, ketoprofen, naproxen, fenoprofen and flurbiprofen.
The preparation method of the metal organic framework composite material chiral liquid chromatography stationary phase based on the post-modification technology comprises the following steps:
(1) 3-aminopropyl triethoxysilane as coupling agent in SiO2Introducing amino groups on the surface;
(2) using succinic anhydride as modifier to aminate SiO2Introducing carboxyl on the surface;
(3) preparing MOF-NH by using soluble metal salt and organic ligand containing amino active sites as raw materials through a liquid phase epitaxy method2@SiO2；
(4) Adding the MOF-NH obtained in the step (3)2@SiO2A central bond into a chiral site;
(5) activating the material obtained in the step (4) to remove other solvent molecules in the MOFs pore channels; dispersing the activated material in methanol, and filling the material into a chromatographic column by using a column filling machine to obtain the chiral liquid chromatographic stationary phase of the metal organic framework composite material.
By adjusting metal salt and organic ligand with SiO2The thickness of the shell layer can be effectively adjusted, the pore diameter of the shell layer can be effectively changed by changing the types of the metal salt and the organic ligand, and different types of MOFs materials can be obtained by changing the types of the chiral ligand.
Prepared MOFs @ SiO2The composite material has the advantages of larger specific surface area of MOFs material, adjustable pore canal and particle size, modifiable framework and the like, and SiO2Has excellent chromatographic performance and good application prospect.
Prepared chiral MOFs @ SiO2Has different pore sizes and chiral sites, and can have different recognition capabilities on racemes with different structures.
As mentioned above, the direct synthesis method uses chiral compounds as organic frameworks to coordinate and connect with metal ions, and can obtain higher chiral ligand density, but because the chiral molecules are asymmetric structures, the MOFs crystal formed by the method has non-uniform morphology and poor chromatographic stability, and the application of the MOFs crystal in chiral chromatographic resolution is limited.
Research results show that the chiral post-modification method is to modify chiral molecules on the surface of the MOFs on an achiral MOFs framework so as to introduce a chiral function, the method keeps the crystallinity of the MOFs and well solves the problem of poor stability. The method has another advantage that chiral sites can be rationally designed according to the needs of chiral resolution, so that the needs of chiral resolution under different conditions are met. In addition, the MOFs material and the silica material with excellent chromatographic performance form a shell-core structure by using a self-assembly method, and the resolution performance and the fluid performance of the MOFs as a chromatographic stationary phase can be further improved. Therefore, the metal organic framework composite material chiral chromatographic stationary phase based on the post-modification technology has good application prospect in chiral chromatographic resolution.
Example III
The present invention is further illustrated by the following figures and examples. The experimental methods described below are, unless otherwise specified, all routine laboratory procedures. The experimental materials described below, unless otherwise specified, are commercially available.
The detection and analysis methods used in the following examples:
(1) MOFs and SiO were measured using an X-ray powder diffractometer model D8 Advance (Bruker, Germany)2@ MOFs XRD analysis was performed.
(2) MOFs and SiO were analyzed using a Bruker Vertex 80 v Fourier transform infrared spectrometer (Bruker, Germany) with a DTGS detector (16 consecutive scans) on MOFs2@ MOFs FT-IR analysis was performed.
(3) Using a JSM-7401F type scanning electron microscope (JEOL)]For MOFs and SiO2@ MOFs for SEM analysis.
(4) The particle size distribution of the liquid chromatography stationary phase based on a metal organic framework composite was analyzed using a mastressizer model 2000 laser particle sizer (malvern instruments ltd, uk).
(5) The shell thickness is calculated by subtracting the diameter of the silicon spheres from the particle size distribution measurement result.
(6) The specific surface area and the pore diameter of the liquid chromatogram fixed phase based on the metal organic framework composite material are measured by adopting an autosorbiQ type full-automatic specific surface area and porosity analyzer (Congta instruments, USA).
(7) Liquid chromatography was carried out by using LC-20AT high performance liquid chromatography (Shimadzu, Japan).
Example 1: chiral liquid chromatography stationary phase for preparing metal organic framework composite material based on post-modification technology
(1)SiO2Amination of (a): using (amino silanization reagent) as coupling agent and SiO with particle size of 5 μm2Uses silica gel coupling method to prepare aminated SiO as nucleus2: 1g of SiO2Adding into 30mL of anhydrous ethanol, stirring for 60min, adding 1mL of 3-aminopropyltriethoxysilane, heating to 70 deg.C, and stirring for 24 h. After the reaction is finished, washing the reaction product with absolute ethyl alcohol for three times. After centrifugation, the product is placed in a vacuum drying oven at 70 DEG CVacuum drying for 8 h.
(2)SiO2Carboxylation of (a): weighing 2g succinic anhydride, adding into 20mL DMF, stirring for dissolving, and 1g aminated SiO2Ultrasonically dispersing in 20mL of DMF, dropwise adding into a succinic anhydride solution, and stirring at room temperature for 24 h. After the reaction is finished, washing the reaction product with DMF three times, and washing the reaction product with absolute ethyl alcohol three times. After centrifugation, the product was dried in a vacuum oven at 70 ℃ for 8 h.
(3)MOF-NH2@SiO2The preparation of (1): 1mmol of ZrCl4 was dissolved ultrasonically in 50mL of DMF and 0.1g of carboxylated SiO was added21mmol of aminobiphenyldicarboxylic acid was dissolved in 50mL of DMF by sonication, 2mL of acetic acid was added, and the mixture was mixed with the above solution and stirred for 72 hours. With DMF and CH, respectively2Cl2Cleaning twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr to obtain metal organic framework composite material with amino group;
(4)MOF-NH2@SiO2chiral post-modification of (2): 0.1g of MOF-NH is weighed2@SiO2Ultrasonically dispersing the mixture in 20mL of absolute ethyl alcohol, dropwise adding 70 mu L of (R) -1, 2-epoxy ethyl benzene, adjusting the pH to 8, and stirring the mixture at room temperature for 12 hours. Washing with anhydrous ethanol twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr. The chiral liquid chromatography stationary phase of the metal organic framework composite material can be obtained.
Example 2: chiral liquid chromatography stationary phase for preparing metal organic framework composite material based on post-modification technology
(1)SiO2Amination of (a): the same as example 1;
(2)SiO2carboxylation of (a): the same as example 1;
(3)MOF-NH2@SiO2the preparation of (1): 0.6mmol of AlCl3·6H2O was dissolved in 150mL of DMF by sonication, poured into 50mL of DMF containing 0.5g of silicon-carboxylated spheres, stirred for 1 hour, 0.9mmol of 2-aminoterephthalic acid was dissolved in 200mL of DMF by sonication, mixed with the above solution, and stirred for 72 hours. With DMF and CH, respectively2Cl2Cleaning twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr. So as to obtain the liquid chromatogram fixed phase of the metal organic framework composite material;
(4)MOF-NH2@SiO2chiral post-modification of (2): weighing 4.3mmol of trispyrrolidinylphosphonium bromide hexafluorophosphate, ultrasonically dissolving in 100mL of dichloromethane, dropwise adding 500 mu L of (S) -2-phenylpropionic acid, and weighing 0.5g of MOF-NH2@SiO2And 8.5mmol of 4-dimethylaminopyridine were dispersed with sonication in 50mL of dichloromethane and stirred at room temperature for 48 h. Washed twice with dichloromethane and dried in a vacuum drying oven at 40 ℃ for 8 h. The chiral liquid chromatography stationary phase of the metal organic framework composite material can be obtained.
Example 3: chiral liquid chromatography stationary phase for preparing metal organic framework composite material based on post-modification technology
(1)SiO2Amination of (a): the same as example 1;
(2)SiO2carboxylation of (a): the same as example 1;
(3)MOF-NH2@SiO2the preparation of (1): 1mmol of ZrCl4 was ultrasonically dissolved in 50mL of DMF, 0.1g of carboxylated SiO2 was added, 1mmol of amino terephthalic acid was ultrasonically dissolved in 50mL of DMF, 2mL of acetic acid was added, and the mixture was mixed with the above solution and stirred for 72 hours. With DMF and CH, respectively2Cl2Cleaning twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr to obtain metal organic framework composite material with amino group;
(4)MOF-NH2@SiO2chiral post-modification of (2): 0.1g of MOF-NH is weighed2@SiO2Ultrasonically dispersing the mixture in 20mL of absolute ethyl alcohol, dropwise adding 70 mu L of (R) -1, 2-epoxy ethyl benzene, adjusting the pH to 8, and stirring the mixture at room temperature for 12 hours. Washing with anhydrous ethanol twice, and vacuum drying in a vacuum drying oven at 40 deg.C for 8 hr. The chiral liquid chromatography stationary phase of the metal organic framework composite material can be obtained.
Example 4: chiral liquid chromatography stationary phase for preparing metal organic framework composite material based on post-modification technology
(1)SiO2Amination of (a): the same as example 1;
(2)SiO2carboxylation of (a): the same as example 1;
(3)MOF-NH2@SiO2the preparation of (1): 0.6mmol of CrCl3Ultrasonic dissolving in 150mL of DMF was poured into 50mL of DMF containing 0.5g of silicon carbide beads, stirred for 1 hour, 0.9mmol of 2-aminoterephthalic acid was dissolved in 200mL of DMF by sonication, and then mixed with the above solution, and stirred for 72 hours. With DMF and CH, respectively2Cl2Cleaning twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr. The liquid chromatogram fixed phase of the metal organic framework composite material can be obtained.
(4)MOF-NH2@SiO2Chiral post-modification of (2): 6mmol of trispyrrolidinylphosphonium bromide hexafluorophosphate is weighed, ultrasonically dispersed in 200mL of absolute ethanol, 6.4mmol (L) -tartaric acid is added, and 0.5g of MOF-NH is weighed2@SiO2And 12mmol of 4-dimethylamino pyridine are ultrasonically dispersed in 50mL of absolute ethyl alcohol, stirred for 96h at room temperature, washed with absolute ethyl alcohol for three times, and placed in a vacuum drying oven at 70 ℃ for vacuum drying for 8h to obtain the chiral liquid chromatography stationary phase of the metal organic framework composite material.
Example 5: chiral liquid chromatography stationary phase for preparing metal organic framework composite material based on post-modification technology
(1)SiO2Amination of (a): the same as example 1;
(2)SiO2carboxylation of (a): the same as example 1;
(3)MOF-NH2@SiO2the preparation of (1): adding 0.6mmol of FeCl3·6H2O was dissolved in 150mL of DMF by sonication, poured into 50mL of DMF containing 0.5g of silicon-carboxylated spheres, stirred for 1 hour, 0.9mmol of 2-aminoterephthalic acid was dissolved in 200mL of DMF by sonication, mixed with the above solution, and stirred for 72 hours. With DMF and CH, respectively2Cl2Cleaning twice, and vacuum drying in a vacuum drying oven at 60 deg.C for 8 hr. The liquid chromatogram fixed phase of the metal organic framework composite material can be obtained.
(4)MOF-NH2@SiO2Chiral post-modification of (2): weighing 6mmol of trispyrrolidinylphosphonium bromide hexafluorophosphate, ultrasonically dispersing in 200mL of absolute ethanol, adding 6.4mmol of (D) -camphoric acid, weighing 0.5g of MOF-NH2@SiO2And 12mmol of 4-dimethylamino pyridine are ultrasonically dispersed in 50mL of absolute ethyl alcohol, stirred for 96 hours at room temperature, washed with the absolute ethyl alcohol for three times and placed in a vacuum drying oven at 70 ℃ for vacuumDrying for 8h to obtain the chiral liquid chromatography stationary phase of the metal organic framework composite material.
Example 6: detecting chromatographic performance of chiral liquid chromatography stationary phase of metal organic framework composite material based on post-modification technology
(1) Chiral MOFs @ SiO2And (3) material structure characterization:
FIG. 1 shows MOFs and MOFs @ SiO2XRD contrast pattern of (a); FIG. 2 is SiO2And MOFs @ SiO2FT-IR diagram of (1); FIG. 3 is MOFs @ SiO2SEM image of (5), FIG. 4 is MOFs @ SiO2N of (A)2Adsorption and desorption isotherm diagram.
(2) Chromatographic performance:
selection of ketoprofen as representative of the Arylpropionic acid racemate in the non-steroidal drug vs. MOFs @ SiO prepared in example 12The chiral chromatographic stationary phase is used for carrying out chromatographic performance determination. The operation steps of the determination are as follows:
packing of chromatographic column: the column was packed by homogenization. Weighing 1g of MOFs @ SiO2Dispersing in 50mL methanol for 20min under ultrasonic stirring, filling into 100mm × 2.1mm chromatographic column with methanol as mobile phase under 40MPa, maintaining for 50min, reducing pressure, standing for 10min, and removing the column tube. Before the chromatographic experiment was performed, the column was washed with methanol until the baseline was smooth.
Ketoprofen standard solution: 10mL of a 1mg mL-1 solution was prepared using methanol as a solvent.
A liquid chromatography analysis method:
mobile phase: methanol (v): water (v) 95: 5; detection wavelength: 254 nm; flow rate: 0.1mL min-1(ii) a Column temperature: 40 ℃, sample introduction: 2L.
Fig. 5 is a liquid chromatogram of ketoprofen.
(3) Chromatographic performance:
selection of Methylbenzaminomethane as representative of aromatic racemates in pharmaceutical intermediates for the MOFs @ SiO prepared in example 22The chiral chromatographic stationary phase is used for carrying out chromatographic performance determination. The operation steps of the determination are as follows:
packing of chromatographic column: is packaged by a homogenate methodAnd (4) filling a chromatographic column. Weighing 1g of MOFs @ SiO2Dispersing in 50mL n-hexane/isopropanol (v/v, 95:5) under ultrasonic stirring for 20min, filling the material into a chromatographic column of 100mm × 2.1mm under 40MPa with n-hexane/isopropanol (v/v, 95:5) as mobile phase, maintaining for 50min, reducing pressure, standing for 10min, and discharging the chromatographic column tube. Before carrying out the chromatographic experiments, the column was washed with n-hexane/isopropanol (v/v, 95:5) until the baseline was smooth.
Methylbenzylamine standard solution: 1 mg/mL of n-hexane/isopropyl alcohol (v/v, 95:5) was prepared as a solvent-110mL of the solution (2).
A liquid chromatography analysis method:
mobile phase: n-hexane (v): isopropanol (v) ═ 95: 5; detection wavelength: 210 nm; flow rate: 0.3 mL/min-1(ii) a Column temperature: 40 ℃, sample introduction: 2 μ L.
FIG. 6 is a liquid chromatogram of methylbenzylamine.
Methylbenzylamine was continuously fed 10 times under the same liquid chromatography conditions, and the results are shown in Table 1.
TABLE 1
| Number of times | tR1 | S1 | tR2 | S2 |
| 1 | 5.488 | 25881728 | 7.253 | 20988605 |
| 2 | 5.468 | 25303957 | 7.247 | 20423529 |
| 3 | 5.436 | 25166409 | 7.209 | 20469148 |
| 4 | 5.46 | 25365644 | 7.159 | 20458674 |
| 5 | 5.45 | 25348397 | 7.135 | 20467770 |
| 6 | 5.487 | 25760885 | 7.2 | 20812901 |
| 7 | 5.465 | 25428954 | 7.17 | 20568197 |
| 8 | 5.537 | 26110969 | 7.329 | 21095004 |
| 9 | 5.54 | 25822517 | 7.264 | 20758649 |
| 10 | 5.468 | 25549193 | 7.176 | 20635588 |
| Mean value of | 5.4799 | 25573865.3 | 7.2142 | 20667806.5 |
| Standard deviation of | 0.034497826 | 304546.1215 | 0.058879915 | 237711.7629 |
| Relative Standard Deviation (SD) | 0.006295339 | 0.01190849 | 0.008161669 | 0.011501548 |
As can be seen from Table 1, the retention time and the Relative Standard Deviation (RSD) of the peak area of methylbenzylamine, which is continuously injected 10 times under the same liquid chromatography condition, are both around 1%, indicating that the above MOFs @ SiO2The chiral chromatographic fixation has good repeatability and chromatographic stability relative to the analysis result.
It should be noted that the above-mentioned embodiments are only for explaining the present invention, and do not constitute any limitation to the present invention. The present invention has been described with reference to exemplary embodiments, but the words which have been used herein are words of description and illustration, rather than words of limitation. The invention can be modified, as prescribed, within the scope of the claims and without departing from the scope and spirit of the invention. Although the invention has been described herein with reference to particular means, materials and embodiments, the invention is not intended to be limited to the particulars disclosed herein, but rather extends to all other methods and applications having the same functionality.
Claims (10)
1. A chiral liquid chromatography stationary phase of a metal organic framework composite material based on a post-modification technology comprises SiO2A core, and coated in SiO2The MOFs layer is coated on the outer surface of the core, wherein the MOFs layer is coated on the SiO by a liquid phase epitaxy method2And (3) bonding a chiral ligand on the MOFs layer by utilizing a post-modification technology.
2. The chiral liquid chromatography stationary phase of claim 1, wherein the SiO is2Has a grain size of 5 μm, and the material constituting the MOFs layer comprises UiO-66-NH2、UiO-67-NH2、MIL-53-NH2And MIL-101-NH2One or more of the above; and/or the thickness of the MOFs layer is 10-1000nm, preferably 100-500 nm.
3. The chiral liquid chromatography stationary phase of claim 1 or 2, wherein: the chiral ligand used for post-modification comprises one or more of L-tartaric acid, L-amino acid, D-camphoric acid, R-epoxyphenylethane and S-2-phenylpropionic acid.
4. A method for preparing a chiral liquid chromatography stationary phase of a metal organic framework composite material based on post-modification technology according to any one of claims 1 to 3, comprising:
step A, towards SiO2Adding coupling agent into the dispersion, stirring, reacting, washing, centrifugally separating and drying to obtain aminated SiO2；
Step B, amination SiO2Adding the dispersion into succinic anhydride solution, stirring, reacting, washing and drying to obtain carboxylated SiO2；
Step C, carboxylating SiO containing soluble metal salt2Mixing the dispersion liquid with the organic ligand solution, stirring, reacting, washing, activating and drying to obtain the metal-organic framework composite material;
and D, adding the metal organic framework composite material solution into the chiral ligand solution, stirring, reacting, washing and drying to obtain the chiral chromatographic stationary phase of the metal organic framework composite material based on the post-modification technology.
5. The method of claim 4, wherein: in the step D, the chiral ligand solution is prepared by dissolving the chiral ligand in an organic solvent; the concentration of the chiral ligand solution is 1-40 mmol/L; the chiral ligand comprises one or more of L-tartaric acid, D-camphoric acid, R-epoxyphenylethane and S-2-phenylpropionic acid; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
6. The method of claim 4, wherein: in step D, optionally adding a carboxyl protecting agent into the chiral ligand solution before mixing the chiral ligand solution and the metal organic framework material solution; preferably, the molar ratio of the chiral ligand to the carboxyl-containing protective agent is 1 (0-4); and/or, the carboxy protecting agent includes, but is not limited to, a trispyrrolidinyl phosphonium bromide hexafluorophosphate salt.
7. The method of claim 4, wherein: in the step D, the metal organic framework composite material solution is prepared by dissolving a metal organic framework composite material in an organic solvent; the concentration of the metal organic framework composite material solution is 1-20 mg/L; preferably, the concentration of the metal organic framework composite material solution is 8-15 mg/L; the organic solvent comprises one or more of absolute ethyl alcohol and dichloromethane.
8. The method of claim 4, wherein: in step D, optionally adding a catalyst to the metal organic framework composite solution; the mass ratio of the metal organic framework composite material to the catalyst is 1 (0-3); preferably, the catalyst comprises 4-dimethylaminopyridine.
9. The method of claim 4, wherein: in the step D, the mass ratio of the chiral ligand to the chiral metal organic framework material is 1: (0.5-5). The stirring speed is 100-800 rpm; and/or the temperature of the reaction is room temperature; and/or the reaction time is 12-168 hours, preferably 12-120 hours; and/or, in step D, washing with ethanol, vacuum drying at 80 ℃, activating in dichloromethane solution for 6-96 hours, and finally vacuum drying at 100 ℃.
10. Use of the liquid chromatography stationary phase of a metal organic framework composite material based on post-modification technology according to any one of claims 1 to 3 or the liquid chromatography stationary phase of a metal organic framework composite material based on post-modification technology prepared by the method according to any one of claims 4 to 10 for the chromatographic resolution of aromatic racemates used as pharmaceutical intermediates and arylpropionic acid racemates used as non-steroidal drugs; preferably, the aromatic raceme used as the pharmaceutical intermediate comprises one or more of 1-phenyl ethanol, methyl benzylamine, mandelic acid and 1- (1-naphthyl) ethanol; the raceme of arylpropionic acid used as non-steroid medicine includes one or several kinds of ibuprofen, ketoprofen, naproxen, fenoprofen and flurbiprofen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111340994.8A CN114146696A (en) | 2021-11-12 | 2021-11-12 | Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111340994.8A CN114146696A (en) | 2021-11-12 | 2021-11-12 | Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114146696A true CN114146696A (en) | 2022-03-08 |
Family
ID=80459784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111340994.8A Pending CN114146696A (en) | 2021-11-12 | 2021-11-12 | Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114146696A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115490878A (en) * | 2022-10-27 | 2022-12-20 | 南开大学 | Metal-organic framework material with chiral defect and construction method and application thereof |
| CN115678026A (en) * | 2022-10-25 | 2023-02-03 | 华南理工大学 | Chiral functionalized modified MOFs adsorbent, preparation method and application thereof in resolution of nicotine enantiomer |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417227A (en) * | 2008-10-31 | 2009-04-29 | 北京化工大学 | Silica gel bonded double-chirality active center chromatogram filler, preparation method and use thereof |
| US20120227469A1 (en) * | 2009-12-21 | 2012-09-13 | Dow Global Technologies Llc | Chromatography of polyolefin polymers |
| CN105148882A (en) * | 2015-06-30 | 2015-12-16 | 河北大学 | Core-shell type hydrophilic chromatographic stationary phase with metal organic framework material as shell, preparation method and application thereof |
| CN106166482A (en) * | 2016-07-07 | 2016-11-30 | 安庆师范大学 | The preparation and application of novel chiral MOF skeleton chromatographic column |
| CN106496025A (en) * | 2014-09-03 | 2017-03-15 | 阿卜杜拉阿齐兹国王科技城 | A kind of same chiral metal organic frame compound with enantiomerism scapus [5] aromatic hydrocarbons activity domain |
| CN111821960A (en) * | 2020-07-24 | 2020-10-27 | 北京工商大学 | Liquid chromatography stationary phase based on metal organic framework composite material and preparation method thereof |
| CN112898585A (en) * | 2021-01-22 | 2021-06-04 | 盐城工学院 | Chiral metal-organic framework material and application thereof in chiral chromatographic column |
| CN112973655A (en) * | 2019-12-02 | 2021-06-18 | 中国科学院大连化学物理研究所 | Ion exchange chromatography stationary phase and preparation and application thereof |
| CN113061264A (en) * | 2021-04-19 | 2021-07-02 | 郑州大学 | Chiral MOFs material and application thereof as chromatographic stationary phase in chiral drug resolution |
-
2021
- 2021-11-12 CN CN202111340994.8A patent/CN114146696A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417227A (en) * | 2008-10-31 | 2009-04-29 | 北京化工大学 | Silica gel bonded double-chirality active center chromatogram filler, preparation method and use thereof |
| US20120227469A1 (en) * | 2009-12-21 | 2012-09-13 | Dow Global Technologies Llc | Chromatography of polyolefin polymers |
| CN106496025A (en) * | 2014-09-03 | 2017-03-15 | 阿卜杜拉阿齐兹国王科技城 | A kind of same chiral metal organic frame compound with enantiomerism scapus [5] aromatic hydrocarbons activity domain |
| CN105148882A (en) * | 2015-06-30 | 2015-12-16 | 河北大学 | Core-shell type hydrophilic chromatographic stationary phase with metal organic framework material as shell, preparation method and application thereof |
| CN106166482A (en) * | 2016-07-07 | 2016-11-30 | 安庆师范大学 | The preparation and application of novel chiral MOF skeleton chromatographic column |
| CN112973655A (en) * | 2019-12-02 | 2021-06-18 | 中国科学院大连化学物理研究所 | Ion exchange chromatography stationary phase and preparation and application thereof |
| CN111821960A (en) * | 2020-07-24 | 2020-10-27 | 北京工商大学 | Liquid chromatography stationary phase based on metal organic framework composite material and preparation method thereof |
| CN112898585A (en) * | 2021-01-22 | 2021-06-04 | 盐城工学院 | Chiral metal-organic framework material and application thereof in chiral chromatographic column |
| CN113061264A (en) * | 2021-04-19 | 2021-07-02 | 郑州大学 | Chiral MOFs material and application thereof as chromatographic stationary phase in chiral drug resolution |
Non-Patent Citations (1)
| Title |
|---|
| WEN-TING KOU ET AL.: "Post-synthetic modification of metal–organic frameworks for chiral gas chromatography", J. MATER. CHEM. A, vol. 6, pages 17861 - 17866 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115678026A (en) * | 2022-10-25 | 2023-02-03 | 华南理工大学 | Chiral functionalized modified MOFs adsorbent, preparation method and application thereof in resolution of nicotine enantiomer |
| CN115678026B (en) * | 2022-10-25 | 2023-08-18 | 华南理工大学 | Chiral functionalized modified MOFs adsorbent and preparation and application thereof in resolution of nicotine enantiomer |
| CN115490878A (en) * | 2022-10-27 | 2022-12-20 | 南开大学 | Metal-organic framework material with chiral defect and construction method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114146696A (en) | Metal organic framework composite material chiral chromatography stationary phase based on post-modification technology | |
| CN111821960A (en) | Liquid chromatography stationary phase based on metal organic framework composite material and preparation method thereof | |
| Liu et al. | A review on the use of ionic liquids in preparation of molecularly imprinted polymers for applications in solid-phase extraction | |
| Yoshimatsu et al. | Uniform molecularly imprinted microspheres and nanoparticles prepared by precipitation polymerization: The control of particle size suitable for different analytical applications | |
| Zhang et al. | Chiral porous organic frameworks and their application in enantioseparation | |
| TWI303187B (en) | Improved solid media | |
| CN104014320B (en) | A kind of aqueous metal organic frame molecular engram material of enriched with trace meta-tolyl-N-methylcarbamate (MTMC) | |
| Cui et al. | Facile construction of magnetic hydrophilic molecularly imprinted polymers with enhanced selectivity based on dynamic non-covalent bonds for detecting tetracycline | |
| CN105664880B (en) | The preparation method of graphene oxide/boronate metal organic frame/polyurethane material | |
| CN109569521B (en) | Rhodanine functionalized MOFs adsorbent and preparation method and application thereof | |
| CN103570871A (en) | Mesoporous molecular sieve SBA-15 composite nano surface imprinted polymer and preparation method thereof | |
| CN112121853B (en) | Mesoporous hollow silica nanosphere loaded with prolinol catalyst as well as preparation method and application of mesoporous hollow silica nanosphere | |
| CN113292735B (en) | Simple preparation method of hollow ZIF-8 material | |
| CN110064372A (en) | A kind of metal organic framework magnetic composite and its preparation method and application | |
| CN114213562A (en) | Preparation method of magnetic polystyrene microspheres with different particle sizes | |
| CN108129669A (en) | A kind of salen porous organic polymers and metal complex and application | |
| Wang et al. | Synthesis of a molecularly imprinted polymer on NH2-MIL-101 (Cr) for specific recognition of diclofenac sodium | |
| CN105153367A (en) | Preparation method of dicyandiamide mesoporous surface molecularly imprinted polymer microspheres | |
| CN106040204A (en) | Magnetic microporous organic nanotube hybrid material and preparation and application thereof | |
| CN108586660A (en) | The preparation method of TNT magnetic molecularly imprinted polymer microballoons | |
| CN109647002B (en) | MOF @ SiO for enantiomer resolution2Core-shell microsphere HPLC chiral column | |
| CN109762080A (en) | A kind of supermolecule chirality porous polymer separating medium and preparation method and application | |
| CN111909311A (en) | Zearalenone functionalized graphene surface molecularly imprinted material and preparation method thereof | |
| CN101176853B (en) | Chirality diamine-metallic complex polyphase catalyzer as well as preparation method and application | |
| CN117024768A (en) | Preparation method of magnetic hydrogen bond organic framework material |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220308 |