CN114671780B - 一种基于柱芳烃的共价有机聚合物及其应用 - Google Patents
一种基于柱芳烃的共价有机聚合物及其应用 Download PDFInfo
- Publication number
- CN114671780B CN114671780B CN202210369815.1A CN202210369815A CN114671780B CN 114671780 B CN114671780 B CN 114671780B CN 202210369815 A CN202210369815 A CN 202210369815A CN 114671780 B CN114671780 B CN 114671780B
- Authority
- CN
- China
- Prior art keywords
- column
- arene
- covalent organic
- p5cofs
- organic polymer
- 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
- 150000004945 aromatic hydrocarbons Chemical class 0.000 title claims abstract description 27
- 229920000620 organic polymer Polymers 0.000 title abstract description 13
- 230000008685 targeting Effects 0.000 claims abstract description 14
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 6
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 5
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 claims description 15
- 229960002918 doxorubicin hydrochloride Drugs 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 238000003745 diagnosis Methods 0.000 claims description 6
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 claims description 6
- -1 amino vitamin Chemical class 0.000 claims description 3
- 229940100684 pentylamine Drugs 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 abstract description 5
- 230000002776 aggregation Effects 0.000 abstract description 4
- 238000004220 aggregation Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 210000004881 tumor cell Anatomy 0.000 abstract description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 2
- 230000008878 coupling Effects 0.000 abstract description 2
- 238000010168 coupling process Methods 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 230000006698 induction Effects 0.000 abstract description 2
- 230000010354 integration Effects 0.000 abstract description 2
- 238000011068 loading method Methods 0.000 abstract description 2
- 238000004020 luminiscence type Methods 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000013310 covalent-organic framework Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 125000003172 aldehyde group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- VTJUKNSKBAOEHE-UHFFFAOYSA-N calixarene Chemical class COC(=O)COC1=C(CC=2C(=C(CC=3C(=C(C4)C=C(C=3)C(C)(C)C)OCC(=O)OC)C=C(C=2)C(C)(C)C)OCC(=O)OC)C=C(C(C)(C)C)C=C1CC1=C(OCC(=O)OC)C4=CC(C(C)(C)C)=C1 VTJUKNSKBAOEHE-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002678 macrocyclic compounds Chemical class 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012621 metal-organic framework Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N 1,4-Benzenediol Natural products OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
- ZSKXYSCQDWAUCM-UHFFFAOYSA-N 1-(chloromethyl)-2-dodecylbenzene Chemical compound CCCCCCCCCCCCC1=CC=CC=C1CCl ZSKXYSCQDWAUCM-UHFFFAOYSA-N 0.000 description 1
- LNSXRXFBSDRILE-UHFFFAOYSA-N Cucurbitacin Natural products CC(=O)OC(C)(C)C=CC(=O)C(C)(O)C1C(O)CC2(C)C3CC=C4C(C)(C)C(O)C(O)CC4(C)C3(C)C(=O)CC12C LNSXRXFBSDRILE-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 150000001904 cucurbitacins Chemical class 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000007210 heterogeneous catalysis Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000013265 porous functional material Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供一种基于柱芳烃的共价有机聚合物及其应用，本发明以乙氧基柱[5]芳烃为原料通过多步有机合成反应将其中一个苯环单元上的两个乙氧基替换为苯氨基，合成了具有刚性支柱的偶联柱[5]芳烃P5NH2，并利用该柱芳烃与聚集诱导发光基元B4CHO制备了共价有机聚合物P5COFs。P5COFs中存在两种空腔，柱芳烃的空腔可以络合靶向基团，共价有机聚合物（COFs）的空腔可以用来负载抗癌药物，在靶向分子的诱导下能有效地将负载的药物送入肿瘤细胞，同时聚集诱导发光基元B4CHO能够实时监测药物在体内的情况，实现诊疗一体化。
Description
技术领域
本发明属于生物医药技术领域，具体涉及一种基于柱芳烃的共价有机聚合物及其应用。
背景技术
共价有机聚合物(COFs)作为新兴的多孔功能性材料，由轻元素(H、C、N、O、B)组成，并通过可逆缩合反应以共价键连接。与通过配位键建立的金属有机骨架(MOF)相比，COF具有重量优势和更高的稳定性。此外，COFs还具有高孔隙率、巨大的比表面积和可设计的有序结构等特点。这些特性使得COFs在能量存储、气体吸附和分离、有机多相催化和化学/生物传感器等方面有着广泛的应用。在最近的几项研究中，纳米级COFs体系被证明是潜在的药物载体，已成功负载了布洛芬、5-氟尿嘧啶或卡托普利等化学药物。
大环化合物，例如环糊精、冠醚、杯芳烃、葫芦素和环烷，已经成为主体-客体化学中不可或缺的部分。柱芳烃是该领域中一类相对较新的大环化合物，其结构与杯芳烃类似，由亚甲基桥连接n个对苯二酚醚或对苯二酚单元的对位构成。自其被发现以来一直稳步发展，已在液晶、人工跨膜通道、纳米颗粒合成及感应中得到应用。当在COFs中引入柱芳烃后，COFs往往会因为柱芳烃优异的主客体化学性质和刚性疏水空腔而对环境条件的变化很敏感，包括pH、光、温度、压力、氧化还原条件、金属阳离子、阴离子、阳离子、溶剂等。因此，柱芳烃的引入可实现COFs更广泛的应用。
发明内容
本发明的目的是提供一种基于柱芳烃的共价有机聚合物及其应用。
为了实现上述目的，本发明提供如下技术方案：
一种基于柱芳烃的共价有机聚合物，所述基于柱芳烃的共价有机聚合物结构式如下式所示：
上述基于柱芳烃的共价有机聚合物在制备肿瘤诊疗试剂中的应用。
一种肿瘤诊疗试剂，包括上述基于柱芳烃的共价有机聚合物。
进一步地，还包括靶向基团和抗癌药物。
更进一步地，所述靶向基团为靶向基团BIO，所述抗癌药物为DOX。
本发明的有益效果：本发明以乙氧基柱[5]芳烃为原料通过多步有机合成反应将其中一个苯环单元上的两个乙氧基替换为苯氨基，合成了具有刚性支柱的偶联柱[5]芳烃P5NH2，并利用该柱芳烃与聚集诱导发光基元B4CHO制备了共价有机聚合物P5COFs。P5COFs中存在两种空腔，柱芳烃的空腔可以络合靶向分子5-(氨基维生素)戊胺(BIO)，COFs的空腔可以负载抗癌药物盐酸阿霉素(DOX)，在靶向分子BIO的诱导下能有效地将负载的药物送入肿瘤细胞，同时聚集诱导发光基元B4CHO能够实时监测药物在体内的情况，实现诊疗一体化。
附图说明
图1为P5NH2在CDCl3中的核磁共振氢谱；
图2为P5NH2在CDCl3中的核磁共振碳谱；
图3为P5NH2和B4CHO溶于DMSO与反应时间相关的核磁共振氢谱；
图4为实施例制备的P5COFs的SEM图；
图5为实施例制备的P5COFs的粒径分布图；
图6为实施例制备的P5COFs的TEM图；
图7为实施例制备的P5COFs的生物相容性数据图；
图8为实施例制备的P5COFs的抗肿瘤活性数据图。
具体实施方式
下面结合附图和具体实施例对本发明作进一步详细说明，但不应理解为对本发明的限制。在不背离本发明精神和实质的情况下，对本发明方法、步骤或条件所作的修改或替换，均属于本发明的范围。实施例中未注明具体条件的实验方法及未说明配方的试剂均为按照本领域常规条件。
实施例1
1、偶联氨基柱[5]芳烃P5NH2的制备
化合物1-1的合成：将4.45g乙氧基柱[5]芳烃(5.00mmol)溶于100mL二氯甲烷，再加入20mL浓度为0.25M硝酸铈铵水溶液，室温反应20min。反应结束后加入饱和NaHCO3水溶液萃取，有机层用无水Na2SO4干燥，旋转蒸发除去有机溶剂，柱层析(按照体积比为乙酸乙酯∶石油醚＝1∶80)得到化合物1-1。
化合物1-2的合成：将1.00g化合物1-1(1.20mmol)溶于100mL二氯甲烷，再加入20mL浓度为0.15M的连二亚硫酸钠水溶液，室温反应4h。反应结束后加入饱和NaCl水溶液萃取，有机层用无水Na2SO4干燥，旋转蒸发除去有机溶剂，得到化合物1-2。
化合物1-3的合成：将1.00g化合物1-2(1.20mmol)溶于100mL二氯甲烷，再加入4mL吡啶和4mL三氟甲磺酸酐，30℃反应12h。反应结束后旋转蒸发除去有机溶剂，柱层析(按照体积比为乙酸乙酯∶石油醚＝1∶50)得到化合物1-3。
化合物P5NH2的合成：将1.10g化合物1-3(1.00mmol)、0.76g的4-氨基苯硼酸(5.55mmol)和0.18g的Pd(PPh3)4(0.16mmol)加入到50mL THF中，再加入30mL浓度为0.20M的K2CO3水溶液，80℃反应24h。反应结束后用水和盐水洗涤，有机层用无水Na2SO4干燥，旋转蒸发除去有机溶剂，柱层析(按照体积比为乙酸乙酯∶石油醚＝1∶30)得到化合物P5NH2。
如图1所示为P5NH2在CDCl3中的核磁共振氢谱，表明该物质所含氢原子数与种类符合预期。
如图2所示为P5NH2在CDCl3中的核磁共振碳谱，表明该物质所含碳原子数与种类符合预期。
2、发光基元B4CHO的制备
将3.2g化合物1(5mmol)、3.35g的4-甲酰基苯硼酸(22.5mmol)、8.29g碳酸钾(60mmol)和285mg的Pd(PPh3)4(0.25mmol)溶于110mL甲苯/水/乙醇的混合溶剂中(甲苯、水与乙醇的体积比为10：1：1)氮气保护下100℃反应72h，冷却至室温后将混合物浓缩，然后用DCM萃取后柱层析(正己烷：DCM＝1：1)，得到B4CHO。
3、基于柱芳烃的COF材料制备
在10mL玻璃瓶中称3mg的B4CHO(0.004mmol)，7.9mg偶联氨基柱[5]芳烃P5NH2(0.008mmol)，溶于1mL DMSO(二甲基亚砜)中，在烘箱中120℃加热12h，反应结束后离心去上清液，取固体烘干得基于柱芳烃的共价有机聚合物材料，命名为P5COFs，具有如下式的结构：
如图3所示为P5NH2和B4CHO溶于DMSO随反应时间延长的核磁共振氢谱，当反应时间为0h时，醛基和氨基的峰较明显，随着反应时间的延长，醛基和氨基逐渐反应，醛基的峰慢慢变小，直到反应时间为10h时醛基的峰消失，证明反应的完成。
基于柱芳烃的COF材料P5COFs的表征：
如图4所示为制得的P5COFs的扫描电镜(SEM)图，由图中可以得到P5COFs产物直径为300nm左右，这同时可以根据图5中的粒径分布图可以得到，大部分产物粒径在303.3nm。
如图6所示为制得的P5COFs的透射电镜(TEM)图，表明制备的P5COFs是粒径在300nm左右的球形。
基于柱芳烃的COF材料P5COFs生物相容性效果测试：
通过将P5COFs、BIO、DOX分散在去离子水中并搅拌24小时可让P5COFs负载DOX并与5-(氨基维生素)戊胺络合，12小时后离心去上清液，将固体真空干燥。并用Hela细胞进行生物相容性实验测试。将COFs分散于培养基(高糖DMEM基液+10％牛血清+5％青霉素)内配成不同浓度的溶液后对细胞进行培养，进而观察细胞在不同浓度下的存活率。
图7中显示了纯COFs和络合了靶向分子的COFs调配不同浓度的培养基在分别培养细胞24小时和48小时的情况下细胞的存活率，可以看到随着浓度的增大细胞的存活率在逐渐的降低，但即使在最大浓度的情况下细胞的存活率依然在80％以上，由此说明该材料属于低毒性材料。
图8为络合BIO和负载DOX后的COFs与纯DOX分别进行的细胞活性研究MTT图，其显示了纯DOX和络合了靶向分子以及DOX的COFs调配不同浓度的培养基在分别培养细胞24小时和48小时的情况下细胞的存活率，可以看到随着药物浓度的增大细胞的存活率在逐渐的降低，同时络合靶向分子并负载了DOX的COFs可以有效的治疗肿瘤HeLa细胞，在最大浓度下，它对细胞的治疗效果优于纯DOX的对照组和只负载了DOX的COFs的对照组。
首先，COFs以及络合靶向分子以后的COF-Bio显示了很好的生物相容性，而进一步负载DOX分子后，相对于纯DOX，本发明的材料显示了更高的肿瘤细胞杀伤性。
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (5)
1.一种基于柱芳烃的COF材料，其结构式如下式所示：
。
2.权利要求1所述基于柱芳烃的COF材料在制备肿瘤诊疗试剂中的应用。
3.一种肿瘤诊疗试剂，其特征在于：包括权利要求1所述基于柱芳烃的COF材料。
4.根据权利要求3所述的肿瘤诊疗试剂，其特征在于：还包括靶向基团和抗癌药物。
5.根据权利要求4所述的肿瘤诊疗试剂，其特征在于：所述靶向基团为5-(氨基维生素)戊胺，所述抗癌药物为盐酸阿霉素。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210369815.1A CN114671780B (zh) | 2022-04-08 | 2022-04-08 | 一种基于柱芳烃的共价有机聚合物及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210369815.1A CN114671780B (zh) | 2022-04-08 | 2022-04-08 | 一种基于柱芳烃的共价有机聚合物及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114671780A CN114671780A (zh) | 2022-06-28 |
| CN114671780B true CN114671780B (zh) | 2023-09-22 |
Family
ID=82078368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210369815.1A Active CN114671780B (zh) | 2022-04-08 | 2022-04-08 | 一种基于柱芳烃的共价有机聚合物及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114671780B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116396488B (zh) * | 2023-03-10 | 2023-11-17 | 浙江大学杭州国际科创中心 | 基于柱芳烃的金属有机框架晶态材料及其制备和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622421A (zh) * | 2016-02-04 | 2016-06-01 | 广西大学 | 苯甲酸柱[5]芳烃酯衍生物的制备方法和应用 |
| CN113004170A (zh) * | 2021-03-05 | 2021-06-22 | 天津孚信阳光科技有限公司 | 一种基于柱[5]芳烃的共价大环聚合物及其制备与应用 |
-
2022
- 2022-04-08 CN CN202210369815.1A patent/CN114671780B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622421A (zh) * | 2016-02-04 | 2016-06-01 | 广西大学 | 苯甲酸柱[5]芳烃酯衍生物的制备方法和应用 |
| CN113004170A (zh) * | 2021-03-05 | 2021-06-22 | 天津孚信阳光科技有限公司 | 一种基于柱[5]芳烃的共价大环聚合物及其制备与应用 |
Non-Patent Citations (1)
| Title |
|---|
| Non-fullerene acceptor engineering with three-dimensional thiophene/selenophene-annulated perylene diimides for high performance polymer solar cells;Li, Gang 等;Journal of Materials Chemistry C: Materials for Optical and Electronic Devices;第06卷(第46期);第12601-12607 页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114671780A (zh) | 2022-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Molla et al. | Silver nanoparticles embedded over porous metal organic frameworks for carbon dioxide fixation via carboxylation of terminal alkynes at ambient pressure | |
| CN108714222B (zh) | 一种新型多功能超分子囊泡的制备与应用 | |
| CN114671780B (zh) | 一种基于柱芳烃的共价有机聚合物及其应用 | |
| CN101092484A (zh) | 一种含膦腈表面改性微球及其制备方法 | |
| Zhou et al. | Modulated covalent organic frameworks with higher specific surface area for the ultrasensitive detection of polybrominated biphenyls | |
| CN107625965B (zh) | 纳米药物载体、包含该纳米药物载体的载药体系及该载药体系的制备方法 | |
| CN110804190A (zh) | 嵌入芳酰胺片段的亲疏水分子自组装胶束及超分子光催化组装体的制备方法 | |
| CN110478318B (zh) | 一种芬顿试剂和阿霉素共转运靶向纳米载体及其制备方法 | |
| Golovanov et al. | Exploiting coupling of boronic acids with triols for a pH-dependent “click-declick” chemistry | |
| Sun et al. | Synthesis and characterization of a water-soluble endohedral metallofullerol | |
| Ravishankar et al. | Rapid, solvent-free synthesis of amorphous, photoluminescent, carbon nanodots from imidazole and maleic anhydride solids | |
| Zhang et al. | Halloysite nanotube-based self-healing fluorescence hydrogels in fabricating 3D cube containing UV-sensitive QR code information | |
| CN106040204B (zh) | 一种磁性微孔有机纳米管杂化材料及其制备和应用 | |
| CN114621159B (zh) | 基于苯并噻二唑的荧光材料、荧光聚合物、荧光纳米粒子以及制备方法和应用 | |
| CN113121396B (zh) | 一种可降解的含二硒基聚多巴胺及其制备方法与应用 | |
| Nguyen et al. | Facile synthesis of novel fluorescent organosilica-coated MOF nanoparticles for fast curcumin adsorption | |
| Tan et al. | Design and synthesis of hollow Ce/Zr-UiO-66 nanoreactors for synergistic and efficient catalysis | |
| Liu et al. | Emulsion interfacial synthesis of hierarchically porous covalent organic framework microcapsules with multilayered boronic acid binding sites for specific molecular separation | |
| CN113185660B (zh) | 一种基于柱芳烃的共价有机骨架及其制备方法和应用 | |
| Tian et al. | Design of a near‐infrared‐triggered photo/thermal dual‐responsive composite carrier with excellent biocompatibility for controllable drug release | |
| CN114470205A (zh) | 一种抗氧化光学活性载纳米金cof材料及其制法、用途 | |
| Fernandes et al. | A post-synthetic modification strategy for the synthesis of pyrene-fused azaacene covalent organic frameworks | |
| Wei et al. | Facile and green preparation of thermal and ph sensitive hydrogel microspheres based on spray drying and the diels–alder reaction | |
| CN109627204A (zh) | 一种含3-甲氧基-4-(5-溴戊氧基)苯基富勒烯吡咯烷的制备方法及应用 | |
| CN113061077B (zh) | α,α-二氘代醇类化合物、氘代药物及其制备方法 |
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 |