CN115109227B - 一种新型多氟荧光聚合物及其制备方法 - Google Patents
一种新型多氟荧光聚合物及其制备方法 Download PDFInfo
- Publication number
- CN115109227B CN115109227B CN202210971004.9A CN202210971004A CN115109227B CN 115109227 B CN115109227 B CN 115109227B CN 202210971004 A CN202210971004 A CN 202210971004A CN 115109227 B CN115109227 B CN 115109227B
- Authority
- CN
- China
- Prior art keywords
- glycol
- polyfluoro
- mixture
- stirring
- acetone
- 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.)
- Active
Links
- 229920001109 fluorescent polymer Polymers 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title abstract description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 60
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 27
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 24
- 239000011737 fluorine Substances 0.000 claims abstract description 24
- 239000012948 isocyanate Substances 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000002513 isocyanates Chemical class 0.000 claims abstract description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 74
- 238000003756 stirring Methods 0.000 claims description 35
- -1 isocyanate compound Chemical class 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- 239000005058 Isophorone diisocyanate Substances 0.000 claims description 16
- NIMLQBUJDJZYEJ-UHFFFAOYSA-N isophorone diisocyanate Chemical compound CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1 NIMLQBUJDJZYEJ-UHFFFAOYSA-N 0.000 claims description 16
- XZNOAVNRSFURIR-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol Chemical compound FC(F)(F)C(O)(C(F)(F)F)C(F)(F)F XZNOAVNRSFURIR-UHFFFAOYSA-N 0.000 claims description 15
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims description 12
- 150000002009 diols Chemical class 0.000 claims description 12
- 229940075420 xanthine Drugs 0.000 claims description 12
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims description 11
- ACCCMOQWYVYDOT-UHFFFAOYSA-N hexane-1,1-diol Chemical compound CCCCCC(O)O ACCCMOQWYVYDOT-UHFFFAOYSA-N 0.000 claims description 11
- UEVVKZOFWMPZAW-UHFFFAOYSA-N 1,1,2,2,3,3,4,4-octafluorohexane-1,6-diol Chemical compound OCCC(F)(F)C(F)(F)C(F)(F)C(O)(F)F UEVVKZOFWMPZAW-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 150000002334 glycols Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- IELVMUPSWDZWSD-UHFFFAOYSA-N 2,2,3,3,4,4-hexafluoropentane-1,5-diol Chemical compound OCC(F)(F)C(F)(F)C(F)(F)CO IELVMUPSWDZWSD-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 238000004945 emulsification Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 3
- 229920005830 Polyurethane Foam Polymers 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000011496 polyurethane foam Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 abstract description 19
- 238000003384 imaging method Methods 0.000 abstract description 14
- 238000001228 spectrum Methods 0.000 abstract description 14
- 239000000126 substance Substances 0.000 abstract description 6
- 239000000523 sample Substances 0.000 abstract description 5
- 238000001514 detection method Methods 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 238000006482 condensation reaction Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000002595 magnetic resonance imaging Methods 0.000 description 5
- 239000013557 residual solvent Substances 0.000 description 5
- 230000001804 emulsifying effect Effects 0.000 description 4
- 239000004814 polyurethane Substances 0.000 description 4
- 229920002635 polyurethane Polymers 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 239000012216 imaging agent Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- JLZUZNKTTIRERF-UHFFFAOYSA-N tetraphenylethylene Chemical group C1=CC=CC=C1C(C=1C=CC=CC=1)=C(C=1C=CC=CC=1)C1=CC=CC=C1 JLZUZNKTTIRERF-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- MKYQPGPNVYRMHI-UHFFFAOYSA-N Triphenylethylene Chemical group C=1C=CC=CC=1C=C(C=1C=CC=CC=1)C1=CC=CC=C1 MKYQPGPNVYRMHI-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000214 effect on organisms Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/751—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring
- C08G18/752—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group
- C08G18/753—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group
- C08G18/755—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group and at least one isocyanate or isothiocyanate group linked to a secondary carbon atom of the cycloaliphatic ring, e.g. isophorone diisocyanate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/2805—Compounds having only one group containing active hydrogen
- C08G18/288—Compounds containing at least one heteroatom other than oxygen or nitrogen
- C08G18/2885—Compounds containing at least one heteroatom other than oxygen or nitrogen containing halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3203—Polyhydroxy compounds
- C08G18/3206—Polyhydroxy compounds aliphatic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3203—Polyhydroxy compounds
- C08G18/3218—Polyhydroxy compounds containing cyclic groups having at least one oxygen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/34—Carboxylic acids; Esters thereof with monohydroxyl compounds
- C08G18/348—Hydroxycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/38—Low-molecular-weight compounds having heteroatoms other than oxygen
- C08G18/3802—Low-molecular-weight compounds having heteroatoms other than oxygen having halogens
- C08G18/3804—Polyhydroxy compounds
- C08G18/3812—Polyhydroxy compounds having fluorine atoms
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/44—Polycarbonates
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6633—Compounds of group C08G18/42
- C08G18/6637—Compounds of group C08G18/42 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/664—Compounds of group C08G18/42 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6633—Compounds of group C08G18/42
- C08G18/6659—Compounds of group C08G18/42 with compounds of group C08G18/34
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/67—Unsaturated compounds having active hydrogen
- C08G18/671—Unsaturated compounds having only one group containing active hydrogen
- C08G18/6715—Unsaturated monofunctional alcohols or amines
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/73—Polyisocyanates or polyisothiocyanates acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/758—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing two or more cycloaliphatic rings
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/14—Macromolecular compounds
- C09K2211/1408—Carbocyclic compounds
- C09K2211/1425—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/14—Macromolecular compounds
- C09K2211/1441—Heterocyclic
- C09K2211/145—Heterocyclic containing oxygen as the only heteroatom
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
本发明涉及一种新型多氟荧光聚合物及其制备方法,以异氰酸酯和二醇的缩合反应为基础,引入含氟功能基团和荧光团,实现多氟荧光聚合物的制备。通过异氰酸酯与二醇的比例,以及亲水基团的引入调节脂水相容性,实现多氟二元醇水性聚合物荧光聚合物的制备。该新型多氟荧光聚合物因其含氟功能团的化学环境近乎一致,使得氟谱半峰宽窄,有效的提高了成像信号强度。此外,荧光团的引入,增加其成像的多样性,将使检测结果更加可靠。该探针在疾病诊断和治疗方面有着较好的应用前景。
Description
技术领域
本发明属于生物与新医药技术合成技术领域,尤其涉及了一种新型多氟荧光聚合物及其制备方法。
背景技术
利用活体成像技术对于疾病进行前期的检测,对疾病诊断和治疗具有重要意义,氟磁共振成像(19F MRI)由于其特异性,在生物成像和疾病诊断等领域受到越来越多的关注。氟成像的优点如下:第一,氟原子有着100%的丰度,自旋量子数为1/2,此外它与氢原子有着非常接近旋磁比(H:42.58 MHz·T–1,F:40.08 MHz·T–1),其敏感性是氢原子的83%(Drug Discov. Today,2008, 13, 473);第二,19F化合物的波谱特性变化范围非常广,而且人体中仅含微量的氟化物,存在于骨骼和牙齿中,它们对含氟造影剂成像的背景影响可以忽略不记(WIREs Nanomed. Nanobiotechnol.2010, 2, 431)。19F MRI的研究可追溯到1977年,由于化学和材料科学的限制,早期氟成像技术研究进展缓。直到最近几年,随着氟化学的快速发展,19F成像研究相关报道呈指数型出现。虽然一些先行者在该领域也做出了一些成绩(Chem. Rev.,2015, 115, 1106;Nano Research,2016, 9(6): 1630),但是离市场的广泛应用还有一定差距。19F MRI示踪剂存在一些共性问题,如:成像剂成像灵敏度和清晰度的问题;成像剂稳定性和生物相容性的问题;成像剂代谢和对生物体的影响等。荧光成像作为一种常用的灵敏度高、成本低的成像手段,近年来,备受化学家们的青睐,开发出一系列新型荧光探针(Nanoscale,2017, 9, 7163;Chin. J. Chem.,2018, 36, 25)。但是荧光成像空间分辨率低,组织渗透性差的缺点一直未被解决。
本发明设计一类新型的示踪剂-具有多氟结构的荧光聚合物,并对其多维成像进行初步探究。把荧光探针、氟核磁成像这两种检测手段有机结合起来,实现多维度呈现同一靶点的情况,将使检测结果更加可靠。
发明内容
为了解决上述现有技术中存在的问题,本发明提供了一种新型多氟荧光聚合物及其制备方法;这一新型荧光聚合物包含两类化学结构,多氟烷基醇封闭型聚氨酯型荧光聚合物和多氟二元醇水性聚合物荧光聚合物。
本发明的目的是这样实现的:
一种新型多氟烷基醇封闭型聚氨酯型荧光聚合物,其具有如下化学结构:
R1为异氰酸酯类化合物的母体结构,R1为:
,/>,/>。
R2为二醇类化合物,包括:己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400。
R3为全氟叔丁醇、(4-(1,2,2-三苯基乙烯基)苯基)甲醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮。
多氟烷基醇封闭型聚氨酯型荧光聚合物的制备方法,其特征在于,包括以下步骤:
1)将2当量的异氰酸酯类化合物溶解于有机溶剂A中,异氰酸酯化合物的溶度范围为:0.3 ~ 3 mmol/mL。
2)将1当量的二醇类化合物和0.001 ~ 0.01当量的催化剂DBTDL溶解于有机溶剂A中,二醇类化合物的溶度范围为:0.2 ~ 2 mmol/mL。混合均匀后,搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中,25 ~ 80℃反应3小时。
3)将2当量的全氟叔丁醇和荧光剂混合物加入反应体系中,全氟叔丁醇和荧光剂的摩尔比为1:0.5~1:0.05,继续搅拌1 ~ 3小时,旋除溶剂即可制得多氟烷基醇封闭型聚氨酯型荧光探针。
所述的反应溶剂A选自丙酮、四氢呋喃、乙腈、环己烷、乙酸乙酯、乙酸甲酯或1,4-二氧六环。优选丙酮或1,4-二氧六环。
本发明的第二个技术方案为多氟二元醇水性聚合物荧光聚合物,其具有如下化学结构:
R1为异氰酸酯类化合物的母体结构,R1为:
R4为二醇类化合物,包括:八氟-1,6-己二醇、1H,1H,10H,10H-全氟-1,10-癸二醇、六氟-1,5-戊二醇、十二氟-1,8-辛二醇、己二醇、乙二醇、丁二醇、T5650E、PEG-200、PEG-400、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2,2-二羟甲基丙酸。
多氟二元醇水性聚合物荧光聚合物的制备方法,其特征在于,包括以下步骤:
1)将2当量的异氰酸酯类化合物溶解于丙酮中,异氰酸酯化合物的溶度范围为:0.3 ~ 3 mmol/mL。
2)将1当量的二醇类化合物的混合物A和0.001 ~ 0.01当量的催化剂DBTDL溶解于丙酮中,二醇类化合物的溶度范围为:0.2 ~ 2 mmol/mL。混合均匀后,搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中,25 ~ 80℃反应2小时。随后加入0.5当量二醇类化合物的混合物B,继续搅拌1小时;接着加入三乙胺搅拌30分钟,最后加入去离子水高速搅拌乳化,旋除溶剂丙酮,即可制得多氟二元醇水性聚合物荧光聚合物。
所述的二醇类化合物的混合物A为含氟二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮和普通二醇(如:己二醇、PEG-200等)三者的混合物。三者的投料摩尔比为:0.3 ~ 1: 0 ~ 0.2 :0 ~ 0.7;
所述的二醇类化合物的混合物B为2,2-二羟甲基丙酸和短脂肪链二醇(如:己二醇、丁二醇等)的混合物,两者的投料摩尔比为:0.1 ~ 0.5: 0.5 ~ 0.9。
积极有益效果:(1)本发明将多氟化合物与荧光分子通过酰胺键选择性的结合起来,实现多维度呈现同一靶点的情况,将使检测结果更加可靠;(2)相比于多氟聚合物,多氟荧光聚合物可以同时获得荧光成像的图像和磁共振图像,通过比对研究为肿瘤临床诊断提供更加准确的影像支撑;(3)这一新型多氟荧光聚合物有着较多的亲水基团,生物相容性好。(4)该多氟荧光聚合物因其含氟功能团的化学环境近乎一致,使得氟谱半峰宽窄,有效的提高了成像信号强度。
附图说明
图1为实施例1中聚合物1的核磁氟谱图片;
图2是实施例3中聚合物3的红外光谱图;
图3是实施例3中聚合物3不同浓度下的荧光强度图谱;
图4是实施例8聚合物8不同浓度下的荧光强度图谱;
图5是聚合物8的19F 365 MHz核磁成像图谱。
具体实施方式
以下为本发明的详细实施步骤:
实施例1
将4.6克(0.02 mol)IPDI溶解于20毫升的丙酮中,将1.18克(0.01 mol)己二醇和0.08克DBTDL催化剂溶解于15毫升的丙酮中,搅拌下把己二醇的丙酮溶液滴加入IPDI溶液中,滴加完毕后室温下反应3小时,称取并加入3.5克(0.015 mol)全氟叔丁醇和1.8克(0.005 mol)(4-(1,2,2-三苯基乙烯基)苯基)甲醇,继续反应2小时,随后旋除溶剂,制得多氟荧光聚合物1。根据投料情况单一的低聚物两端封端剂R3有三种情况:1)都是全氟叔丁醇,2)一端是全氟叔丁醇,一端是四苯乙烯,3)两端都是四苯乙烯(如下式所示)。通过GPC测定,其峰值分子量为3854。红外特征数据如下:IR(cm-1): 3363.03, 2928.26, 1685.31,1658.55, 1533.13, 1462.84,1402.58, 1170.21, 1037.26, 964.9, 788.81, 725.46。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.06(s)。
实施例2
将4.6克(0.02 mol)IPDI溶解于20毫升的丙酮中,将1.18克(0.01 mol)己二醇和0.06克DBTDL催化剂溶解于15毫升的丙酮中,搅拌下把己二醇的丙酮溶液滴加入IPDI溶液中,滴加完毕后室温下反应3小时,称取并加入4.2克(0.018 mol)全氟叔丁醇和0.72克(0.002 mol)(4-(1,2,2-三苯基乙烯基)苯基)甲醇,继续反应2小时,随后旋除溶剂,制得多氟荧光聚合物2。通过GPC测定,其峰值分子量为3798。红外特征数据如下:IR(cm-1):3363.33, 2928.24, 1685.35, 1658.45, 1533.23, 1462.74,1402.58, 1170.29,1037.38, 964.56, 787.1, 725.25。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.08(s)。
实施例3
将4.6克(0.02 mol)IPDI溶解于20毫升的1,4-二氧六环中,将5克(0.01 mol)二醇T5650E和0.04克DBTDL催化剂分散于15毫升的1,4-二氧六环中,搅拌下把T5650E的1,4-二氧六环溶液滴加入IPDI溶液中,滴加完毕后室温下反应3小时,称取并加入4.2克(0.018mol)全氟叔丁醇和0.66克(0.002 mol)3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮,继续反应2小时,随后旋除溶剂,制得多氟荧光聚合物3。根据投料情况单一的低聚物两端封端剂R3有三种情况:1)都是全氟叔丁醇,2)一端是全氟叔丁醇,一端是荧光素,3)两端都是荧光素。通过GPC测定,其峰值分子量为3620。红外特征数据如下:IR(cm-1):3370.84, 2963.78, 2929.38, 1742.68, 1741.93, 1553.45, 1462.59,1261.53,965.93, 801.06, 724.82。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.69(s)。
实施例4
将4.6克(0.02 mol)IPDI溶解于20毫升的四氢呋喃中,将2克(0.01 mol)二醇PEG-200和0.06克DBTDL催化剂分散于15毫升的四氢呋喃中,搅拌下把PEG-200的四氢呋喃溶液滴加入IPDI溶液中,滴加完毕后室温下反应3小时,称取并加入4.2克(0.018 mol)全氟叔丁醇和0.72克(0.002 mol)(4-(1,2,2-三苯基乙烯基)苯基)甲醇,继续反应3小时,随后旋除溶剂,制得多氟荧光聚合物4。通过GPC测定,其峰值分子量为3685。红外特征数据如下:IR(cm-1): 3365.78, 2970.37, 2926.75, 1748.28, 1740.93, 1716.64,1541.12, 1244.08,1109.07, 933.54, 775.36, 646.15。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.48(s)。
实施例5
将3.4克(0.02 mol)HDI溶解于25毫升的丙酮中,将5克(0.01 mol)二醇T5650E和0.05克DBTDL催化剂分散于20毫升的丙酮中,搅拌下把T5650E的丙酮溶液滴加入HDI溶液中,滴加完毕后室温下反应3小时,称取并加入4.2克(0.019 mol)全氟叔丁醇和0.33克(0.001 mol)3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮,继续反应2小时,随后旋除溶剂,制得多氟荧光聚合物5。通过GPC测定,其峰值分子量为3255。红外特征数据如下:IR(cm-1): 3367.93, 2958.43, 2936.12, 1746.39, 1740.08, 1558.72, 1459.37,1239.28, 985.79, 808.32, 736.18。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.57(s)。
实施例6
将5.25克(0.02 mol)HMDI溶解于25毫升的丙酮中,将0.9克(0.01 mol)丁二醇和0.046克DBTDL催化剂分散于10毫升的丙酮中,搅拌下把丁二醇的丙酮溶液滴加入HMDI溶液中,滴加完毕后室温下反应3小时,称取并加入4.2克(0.019 mol)全氟叔丁醇和0.36克(0.001 mol)(4-(1,2,2-三苯基乙烯基)苯基)甲醇,继续反应2.5小时,随后旋除溶剂,制得多氟荧光聚合物6。通过GPC测定,其峰值分子量为3429。红外特征数据如下:IR(cm-1):3737.26, 3614.85, 2922.41, 1696.41, 1675.83, 1544.75, 1054.29,888.13, 795.49,676.02。核磁氟谱数据为:19F NMR(376 MHz, CDCl3)δ -74.55(s)。
实施例7
将4.6克(0.02 mol)IPDI溶解于15毫升的丙酮中,将1.3克(0.005 mol)八氟-1,6-己二醇、0.33克(0.001 mol)荧光素、0.8克(0.004 mol)PEG-200和0.04克DBTDL催化剂分散于15毫升的丙酮中,搅拌下把二醇的混合液滴加入IPDI溶液中,滴加完毕后加热至50度反应2小时,随后加入0.67克(0.005 mol)2,2-二羟甲基丙酸和0.45克(0.005 mol)丁二醇,继续搅拌1小时;接着加入0.1克三乙胺搅拌30分钟,旋除一半溶剂后,加入20毫升的去离子水高速搅拌乳化30分钟,旋除剩余溶剂丙酮,即可制得多氟二元醇水性荧光聚合物7。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定,其峰值分子量为2785。绝干聚合物的红外特征数据如下:IR(cm-1): 3321.71, 2903.01, 1756.39, 1739.28, 1564.16, 1461.52,1357.93,1303.56, 1172.48,1100.56,1043.45,965.93, 843.25,726,725.33。核磁氟谱数据为:19FNMR(376 MHz, DMSO-d6)δ -69.61(s).
实施例8
将4.6克(0.02 mol)IPDI溶解于15毫升的丙酮中,将2.1克(0.008 mol)八氟-1,6-己二醇、0.33克(0.001 mol)荧光素、0.2克(0.001 mol)PEG-200和0.06克DBTDL催化剂分散于15毫升的丙酮中,搅拌下把二醇的混合液滴加入IPDI溶液中,滴加完毕后加热至60度反应2小时,随后加入0.26克(0.002 mol)2,2-二羟甲基丙酸和0.72克(0.008 mol)丁二醇,继续搅拌1小时;接着加入0.1克三乙胺搅拌30分钟,旋除一半溶剂后,加入20毫升的去离子水高速搅拌乳化30分钟,旋除剩余溶剂丙酮,即可制得多氟二元醇水性荧光聚合物8。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定,其峰值分子量为2958。绝干聚合物的红外特征数据相比于实施例7变化不大,具体如下:IR(cm-1): 3321.75, 2903.35, 1756.56, 1739.75,1564.76, 1463.15,1353.68,1301.22, 1164.59,1104.36,1033.69,965.91,842.14,725.59,722.34。核磁氟谱数据为:19F NMR(376 MHz, DMSO-d6)δ -69.43(s).
实施例9
将3.4克(0.02 mol)HDI溶解于15毫升的丙酮中,将2.1克(0.006 mol)十二氟-1,8-辛二醇、0.33克(0.001 mol)荧光素、1.5克(0.003 mol)T5650E和0.06克DBTDL催化剂分散于15毫升的丙酮中,搅拌下把二醇的混合液滴加入IPDI溶液中,滴加完毕后加热至50度反应2小时,随后加入0.26克(0.002 mol)2,2-二羟甲基丙酸和0.72克(0.008 mol)丁二醇,继续搅拌1小时;接着加入0.1克三乙胺搅拌30分钟,旋除一半溶剂后,加入20毫升的去离子水高速搅拌乳化30分钟,旋除剩余溶剂丙酮,即可制得多氟二元醇水性荧光聚合物9。其中R4为十二氟-1,8-辛二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、PEG-200或丁二醇。通过GPC测定,其峰值分子量为2796。绝干聚合物的红外特征数据如下:IR(cm-1): 3330.02, 2961.12, 1719.61, 1635.43, 1657.91, 1557.91,1460.41,1304.80, 1164.59,1086.59,876.74,770.57, 725.53,649.12。核磁氟谱数据为:19FNMR(376 MHz, DMSO-d6)δ -68.79(s).
实施例10
将3.4克(0.02 mol)HDI溶解于15毫升的丙酮中,将2.1克(0.008mol)八氟-1,6-己二醇、0.33克(0.001 mol)荧光素、0.5克(0.001mol)T5650E和0.08克DBTDL催化剂分散于15毫升的丙酮中,搅拌下把二醇的混合液滴加入IPDI溶液中,滴加完毕后加热至50度反应2小时,随后加入0.13克(0.001 mol)2,2-二羟甲基丙酸和0.56克(0.009 mol)乙二醇,继续搅拌1小时;接着加入0.1克三乙胺搅拌30分钟,旋除一半溶剂后,加入20毫升的去离子水高速搅拌乳化30分钟,旋除剩余溶剂丙酮,即可制得多氟二元醇水性荧光聚合物10。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、T5650E或乙二醇。通过GPC测定,其峰值分子量为2689。绝干聚合物的红外特征数据如下:IR(cm-1): 3330.02, 2961.12, 1719.61, 1635.43, 1657.91, 1557.91,1460.41,1304.80,1164.59,1086.59,876.74,770.57, 725.53,649.12。核磁氟谱数据为:19F NMR(376 MHz,DMSO-d6)δ -68.79(s).
实施例11
将3.4克(0.02 mol)HMDI溶解于15毫升的丙酮中,将2.1克(0.008 mol)八氟-1,6-己二醇、0.33克(0.001 mol)荧光素、0.5克(0.001 mol)T5650E和0.06克DBTDL催化剂分散于15毫升的丙酮中,搅拌下把二醇的混合液滴加入HMDI溶液中,滴加完毕后加热至50度反应2小时,随后加入0.13克(0.001 mol)2,2-二羟甲基丙酸和1.05克(0.009 mol)己二醇,继续搅拌1小时;接着加入0.1克三乙胺搅拌30分钟,旋除一半溶剂后,加入20毫升的去离子水高速搅拌乳化30分钟,旋除剩余溶剂丙酮,即可制得多氟二元醇水性荧光聚合物8。其中R4为八氟-1,6-己二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮、2-二羟甲基丙酸、T5650E或己二醇。通过GPC测定,其峰值分子量为2958。绝干聚合物的红外特征数据如下:IR(cm-1): 3733.23, 3623.51, 2935.28, 1768.41,1725.67, 1675.35, 1544.23,1048.34,875.55, 795.49, 647.02。核磁氟谱数据为:19F NMR(376 MHz, DMSO-d6)δ -68.59(s).
荧光强度实验和核磁共振谱实验
称取多氟荧光聚合物3配置质量浓度为20 mg/mL, 10 mg/mL, 5 mg/mL, 1 mg/mL, 0.5 mg/mL, 0.2 mg/mL, 0.1 mg/mL的DMSO溶液各20毫升,测量其荧光强度,测量结果(图3),该探针的荧光强度与聚合物的浓度呈正相关。
称取多氟二元醇水性荧光聚合物8配置质量浓度为50 mg/mL, 10 mg/mL, 5 mg/mL, 2 mg/mL, 1 mg/mL, 0.5 mg/mL, 0.2 mg/mL的DMSO溶液各20毫升,测量其荧光强度,测量结果(图4),该探针的荧光强度与聚合物的浓度呈正相关。
进一步称取多氟二元醇水性荧光聚合物8,用氘代二甲基亚砜配置成浓度为:100mg/mL, 20 mg/mL, 5 mg/mL和1 mg/mL不同浓度的溶液,对其进行体外19F MRI成像效果测试,结果显示(图5),该探针的19F SNR与探针的浓度呈正相关。
本发明的技术方案所公开的技术手段不仅限于上述实施方式所公开的技术手段,还包括由以上技术特征任意组合所组成的技术方案。应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也视为本发明的保护范围。
Claims (3)
1.一种多氟荧光聚合物的制备方法,其特征在于,包括以下步骤: 1)将2当量的异氰酸酯类化合物溶解于有机溶剂A中,异氰酸酯化合物的溶度范围为0.3 ~ 3 mmol/mL;所述的异氰酸酯类化合物为IPDI、HDI或HMDI; 2)将1当量的二醇类化合物和0.001 ~ 0.01当量的催化剂DBTDL溶解于有机溶剂A中,二醇类化合物的溶度范围为0.2 ~ 2 mmol/mL;混合均匀后,搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中,25 ~ 80℃反应3小时; 3)将2当量的全氟叔丁醇和荧光剂混合物加入步骤(2)的反应体系中,全氟叔丁醇和荧光剂的摩尔比为1:0.5~1:0.05,继续搅拌1 ~ 3小时,旋除溶剂即可制得;所述的荧光剂为(4-(1,2,2-三苯基乙烯基)苯基)甲醇。
2.根据权利要求2所述的一种多氟荧光聚合物的制备方法,其特征在于:所述步骤的反应溶剂A选自丙酮、四氢呋喃、乙腈、环己烷、乙酸乙酯、乙酸甲酯或1,4-二氧六环。
3. 一种多氟荧光聚合物的制备方法,其特征在于,包括以下步骤: 1)将2当量的异氰酸酯类化合物溶解于丙酮中,异氰酸酯化合物的溶度范围为0.3 ~ 3 mmol/mL;所述的异氰酸酯类化合物为IPDI、HDI或HMDI; 2)将1当量的二醇类化合物的混合物A和0.001 ~0.01当量的催化剂DBTDL溶解于丙酮中,二醇类化合物的溶度范围为0.2 ~ 2 mmol/mL;混合均匀后,搅拌下把二醇类化合物溶液滴加入异氰酸酯的溶液中,25 ~ 80℃反应2小时;随后加入0.5当量二醇类化合物的混合物B,继续搅拌1小时;接着加入三乙胺搅拌30分钟,最后加入去离子水高速搅拌乳化,旋除溶剂丙酮,即可制得; 所述的二醇类化合物的混合物A为含氟二醇、3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮和普通二醇三者的混合物;三者的投料摩尔比为0.3 ~ 1: 0 ~ 0.2 :0 ~ 0.7;所述含氟二醇为八氟-1,6-己二醇、1H,1H,10H,10H-全氟-1,10-癸二醇、六氟-1,5-戊二醇、十二氟-1,8-辛二醇;所述普通二醇为T5650E、或PEG-200;所述的3',6'-二羟基-3H-螺[异苯并呋喃-1,9'-黄嘌呤]-3-酮用量不为零; 所述的二醇类化合物的混合物B为2,2-二羟甲基丙酸和短脂肪链二醇的混合物,两者的投料摩尔比为0.1 ~ 0.5: 0.5 ~ 0.9;所述的短脂肪链二醇为己二醇、乙二醇或丁二醇。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210971004.9A CN115109227B (zh) | 2022-08-14 | 2022-08-14 | 一种新型多氟荧光聚合物及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210971004.9A CN115109227B (zh) | 2022-08-14 | 2022-08-14 | 一种新型多氟荧光聚合物及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115109227A CN115109227A (zh) | 2022-09-27 |
CN115109227B true CN115109227B (zh) | 2024-01-30 |
Family
ID=83335936
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210971004.9A Active CN115109227B (zh) | 2022-08-14 | 2022-08-14 | 一种新型多氟荧光聚合物及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115109227B (zh) |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102675587A (zh) * | 2012-05-22 | 2012-09-19 | 长春工业大学 | 环境pH响应性聚氨酯荧光发光医用材料的制备 |
CN104164079A (zh) * | 2013-08-14 | 2014-11-26 | 长春工业大学 | 磁性荧光发光pH敏感聚氨酯材料的制备方法 |
CN105770915A (zh) * | 2016-03-02 | 2016-07-20 | 哈尔滨医科大学 | 经呼吸道递送的纳米1h-19f-31p多核磁共振分子成像探针及其制备方法 |
CN108690079A (zh) * | 2018-05-03 | 2018-10-23 | 中国科学院武汉物理与数学研究所 | 一种氟化荧光磷脂及其合成方法和应用 |
CN109529059A (zh) * | 2018-12-26 | 2019-03-29 | 中南大学 | 一种荧光-磁共振双模态量子点及其制备和应用方法 |
CN111269361A (zh) * | 2020-01-20 | 2020-06-12 | 陕西科技大学 | 一种具有荧光性能的含氟丙烯酸酯改性聚氨酯乳液的制备方法 |
CN111808257A (zh) * | 2020-06-16 | 2020-10-23 | 合肥科天水性科技有限责任公司 | 含氟改性室温磷光生物基水性聚氨酯的制备方法和用途 |
CN112812229A (zh) * | 2020-12-31 | 2021-05-18 | 中国科学院苏州纳米技术与纳米仿生研究所 | 一种荧光/mri双模探针及其制备方法与应用 |
CN112851900A (zh) * | 2021-01-14 | 2021-05-28 | 阜阳师范大学 | 香豆素封端的水性聚氨酯及制备方法、水性聚氨酯丙烯酸酯的固化膜的制备方法 |
-
2022
- 2022-08-14 CN CN202210971004.9A patent/CN115109227B/zh active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102675587A (zh) * | 2012-05-22 | 2012-09-19 | 长春工业大学 | 环境pH响应性聚氨酯荧光发光医用材料的制备 |
CN104164079A (zh) * | 2013-08-14 | 2014-11-26 | 长春工业大学 | 磁性荧光发光pH敏感聚氨酯材料的制备方法 |
CN105770915A (zh) * | 2016-03-02 | 2016-07-20 | 哈尔滨医科大学 | 经呼吸道递送的纳米1h-19f-31p多核磁共振分子成像探针及其制备方法 |
CN108690079A (zh) * | 2018-05-03 | 2018-10-23 | 中国科学院武汉物理与数学研究所 | 一种氟化荧光磷脂及其合成方法和应用 |
CN109529059A (zh) * | 2018-12-26 | 2019-03-29 | 中南大学 | 一种荧光-磁共振双模态量子点及其制备和应用方法 |
CN111269361A (zh) * | 2020-01-20 | 2020-06-12 | 陕西科技大学 | 一种具有荧光性能的含氟丙烯酸酯改性聚氨酯乳液的制备方法 |
CN111808257A (zh) * | 2020-06-16 | 2020-10-23 | 合肥科天水性科技有限责任公司 | 含氟改性室温磷光生物基水性聚氨酯的制备方法和用途 |
CN112812229A (zh) * | 2020-12-31 | 2021-05-18 | 中国科学院苏州纳米技术与纳米仿生研究所 | 一种荧光/mri双模探针及其制备方法与应用 |
CN112851900A (zh) * | 2021-01-14 | 2021-05-28 | 阜阳师范大学 | 香豆素封端的水性聚氨酯及制备方法、水性聚氨酯丙烯酸酯的固化膜的制备方法 |
Non-Patent Citations (1)
Title |
---|
Self-delivering Nanoemulsions for Dual Fluorine-19 MRI and Fluorescence Detection;Jelena M. Janjic等;《JACS.》;第130卷;第2832-2841页 * |
Also Published As
Publication number | Publication date |
---|---|
CN115109227A (zh) | 2022-09-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105924394B (zh) | 一种双光子甲醛荧光探针及其制备与应用 | |
JPH05506432A (ja) | Nmr画像化及び分光剤としての↑1↑9f標識化合物 | |
US20120027690A1 (en) | Ph-sensitive graft copolymer, manufacturing method for same, and polymer micelles using method | |
US10869939B2 (en) | Delivery system in micellar form having modular spectral response based on enzyme-responsive amphiphilic PEG-dendron hybrid polymers | |
CN115109227B (zh) | 一种新型多氟荧光聚合物及其制备方法 | |
CN117800951B (zh) | 一种近红外荧光探针及其制备方法与应用 | |
CN114271792B (zh) | 近红外第二窗口检测pH的双通道比率荧光传感器及其制备方法和应用 | |
CN113105488B (zh) | 对粘度响应的共轭bopyin荧光染料的合成方法及应用 | |
CN114907274A (zh) | 5-氟尿嘧啶-1-烷基酸衍生物及制备方法及其应用 | |
Yang et al. | Synthesis and characterization of fluorescent PEG-polyurethane with free carboxyl groups | |
CN108727376A (zh) | 9-氮杂双环[3.3.1]壬烷偶联富碘类化合物及其制备法与用途 | |
CN109593145B (zh) | 一种具有核磁造影功能的环状聚合物及其制备方法和应用 | |
CN114478489B (zh) | 一种氟-19修饰的硝基咪唑化合物及其衍生物的制备方法和应用 | |
CN115109081B (zh) | 一种辣椒素衍生化光敏剂及其制备方法与应用 | |
CN109503770A (zh) | 一种具有高弛豫率的水溶性交联纳米聚合物及其合成方法和用途 | |
US8562953B2 (en) | Dendritic polymers and magnetic resonance imaging contrast agent employing the same | |
CN108250125B (zh) | 一种肿瘤靶向探针化合物及其合成和应用 | |
CN113552099B (zh) | 一种荧光诊断试剂盒及其应用 | |
CN114524809B (zh) | 一种香豆素衍生物及其制备方法和应用 | |
CN115304516B (zh) | 具有非常规发色团的化合物及其制备和应用 | |
CN111704682B (zh) | 一种化合物和纳米胶束 | |
CN111892598B (zh) | 含有苝酰亚胺结构的咪唑类磁性离子液体及其制备方法和应用 | |
JP3060153B2 (ja) | 部分tert−ブトキシ化ポリ(p−ヒドロキシスチレン)の製造方法 | |
CN116903852A (zh) | 一种亲水型骨架含氟聚合物及其制备方法和应用 | |
CN110551263B (zh) | 一种多嵌段聚合物及其合成方法和肿瘤检测用荧光探针 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |