CN106831719A - 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 - Google Patents
一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 Download PDFInfo
- Publication number
- CN106831719A CN106831719A CN201710023290.5A CN201710023290A CN106831719A CN 106831719 A CN106831719 A CN 106831719A CN 201710023290 A CN201710023290 A CN 201710023290A CN 106831719 A CN106831719 A CN 106831719A
- Authority
- CN
- China
- Prior art keywords
- fluorescence
- dendrimers
- naphthalimide
- many pyridine
- application
- 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.)
- Granted
Links
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 239000000412 dendrimer Substances 0.000 title claims abstract description 28
- XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 229920000736 dendritic polymer Polymers 0.000 title claims abstract description 27
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000002776 aggregation Effects 0.000 claims abstract description 16
- 238000004220 aggregation Methods 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000001939 inductive effect Effects 0.000 claims abstract description 11
- 239000004005 microsphere Substances 0.000 claims abstract description 11
- 239000000523 sample Substances 0.000 claims abstract description 9
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 8
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 7
- BYVCTYDTPSKPRM-UHFFFAOYSA-N naphthalene-1-carbonyl naphthalene-1-carboxylate Chemical class C1=CC=C2C(C(OC(=O)C=3C4=CC=CC=C4C=CC=3)=O)=CC=CC2=C1 BYVCTYDTPSKPRM-UHFFFAOYSA-N 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000003384 imaging method Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229940126062 Compound A Drugs 0.000 claims description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 4
- 238000011938 amidation process Methods 0.000 claims description 4
- 238000006482 condensation reaction Methods 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 3
- 238000005292 vacuum distillation Methods 0.000 claims description 3
- 238000007171 acid catalysis Methods 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 1
- 238000004020 luminiscence type Methods 0.000 claims 1
- -1 amino naphthalenes imide Chemical class 0.000 abstract description 8
- 238000001215 fluorescent labelling Methods 0.000 abstract description 4
- 230000003287 optical effect Effects 0.000 abstract description 4
- 238000000799 fluorescence microscopy Methods 0.000 abstract description 3
- 230000008520 organization Effects 0.000 abstract description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 6
- 201000005296 lung carcinoma Diseases 0.000 description 6
- 239000000975 dye Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000013019 agitation Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 125000005909 ethyl alcohol group Chemical group 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 235000011167 hydrochloric acid Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 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
- 230000003213 activating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- JMGZBMRVDHKMKB-UHFFFAOYSA-L disodium;2-sulfobutanedioate Chemical compound [Na+].[Na+].OS(=O)(=O)C(C([O-])=O)CC([O-])=O JMGZBMRVDHKMKB-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000001022 rhodamine dye Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- 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
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
- C09B57/08—Naphthalimide dyes; Phthalimide dyes
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- 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
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1022—Heterocyclic compounds bridged by heteroatoms, e.g. N, P, Si or B
-
- 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
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Physics & Mathematics (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
本发明公开了一种多吡啶萘酰亚胺荧光树形分子(PDPN)，它是由酰胺‑胺中心核连接多个双吡啶甲基氨基萘酰亚胺荧光团，优化组合而得到的聚集诱导发光树形分子。本发明还公开了PDPN的制备方法及其应用。本发明的多吡啶萘酰亚胺树形分子具有优良的聚集诱导荧光性能，可用于水溶性荧光纳米微球的制备，可作为性能优异的荧光染料用于肿瘤细胞的非治疗和诊断目的的荧光成像，该树形分子中多个吡啶甲基氨基萘酰亚胺荧光团具有非键合的超分子相互作用，可作为pH荧光探针，在荧光探针、荧光传感器、生物荧光标记等领域具有重要的应用价值。
Description
技术领域
本发明涉及一种多吡啶萘酰亚胺荧光树形分子(PDPN)及其制备方法和应用，属于荧光化合物及其应用领域。
背景技术
萘酰亚胺衍生物具有较高的荧光量子产率和较大的斯托克斯位移、良好的光稳定性和化学稳定性，在荧光传感及生物荧光分析领域具有重要应用，但现有技术中萘酰亚胺衍生物在聚集态荧光淬灭，且无法在水溶液中使用，生物相容性差，极大限制了其应用范围。对萘酰亚胺进行结构修饰，制备具有聚集诱导荧光，可在水溶液中使用的萘酰亚胺类荧光化合物是近期的研究热点，相关的实验及理论研究受到广泛关注。
具有聚集诱导荧光的多吡啶萘酰亚胺荧光树形分子荧光性能优异，荧光量子效率高，具有优良的聚集诱导荧光性能，可在水溶液中使用，生物相容性好，在现有技术中鲜有报道，可作为性能优良的荧光染料，在荧光传感器、生物荧光分析、荧光标记等领域具有广泛应用价值。
发明内容
技术问题：本发明的目的是提供一种多吡啶萘酰亚胺荧光树形分子，该分子荧光性能优异，荧光量子效率高，具有优良的聚集诱导荧光性能，可在水溶液中使用，生物相容性好；
本发明的第二个目的是提供一种上述该多吡啶萘酰亚胺荧光树形分子的制备方法；
本发明的第三个目的是提供上述多吡啶萘酰亚胺树形分子的应用。
技术方案：本发明提供了一种多吡啶萘酰亚胺聚集诱导荧光树形分子，该分子的结构式如下：
本发明还提供了一种多吡啶萘酰亚胺荧光树形分子的制备方法，该方法包括如下步骤：
1)4-双(2-吡啶甲基)氨基-1，8-萘二甲酸酐PN与酰胺-胺化合物M在无水乙醇中，经三乙胺催化进行酰胺化反应，得到化合物A；
2)化合物A在无水甲醇中经盐酸催化脱保护后，得到化合物B；
3)化合物B在无水乙醇中，经三乙胺催化下与4-双(2-吡啶甲基)氨基-1，8-萘二甲酸酐PN进行酰胺化缩合反应，得到化合物C，之后经过减压蒸馏、柱色谱提纯、重结晶得到权利要求1所述的多吡啶萘酰亚胺荧光树形分子，具体反应式如下：
其中：
步骤1)所述的酰胺化反应的时长为36～48h。
步骤3)所述的酰胺化缩合反应的时长为36～48h。
本发明还提供了多吡啶萘酰亚胺荧光树形分子的应用，该分子应用于聚集诱导发光材料、应用于制备水溶性荧光纳米微球、作为荧光染料应用于肿瘤细胞的非治疗和诊断目的的成像方面、应用于pH荧光探针。
有益效果：与现有技术相比，本发明具有以下优点：
本发明的PDPN是由酰胺-胺中心核连接多个双吡啶甲基氨基萘酰亚胺荧光团，萘酰亚胺为内层单元，氨甲基吡啶为外层端基，优化组合而得到的具有聚集诱导发光树形分子，该分子荧光性能优异，荧光量子效率高。
本发明的PDPN具有优良的聚集诱导性能，可在水溶液中使用，生物相容性好，可用于水溶性荧光纳米微球的制备，可作为性能优异的荧光染料用于肿瘤细胞的非治疗和诊断目的的荧光成像，该树形分子中多个吡啶甲基氨基萘酰亚胺荧光团具有非键合的超分子相互作用，可作为pH荧光探针，在荧光探针、荧光传感器、生物荧光标记等领域具有重要的应用价值。
附图说明
图1为PDPN的固体荧光光谱；
图2为PDPN负载的二氧化硅荧光纳米微球在纯水中的荧光光谱；
图3为PDPN负载的二氧化硅荧光纳米微球的TEM透射电镜照片；
图4为PDPN与肺癌细胞A-549共同孵化后的激光共聚焦荧光成像照片；
图5为PDPN的荧光强度在不同pH下的变化趋势图。
具体实施方式
实施例1：PDPN的制备方法
化合物4-双(2-吡啶甲基)氨基-1，8-萘二甲酸酐(PN)的制备：按文献(JianfengLiu,Ying Qian.A novel naphthalimide-rhodamine dye:Intramolecular fluorescenceresonance energy transfer and ratiometric chemodosimeter for Hg2+and Fe3+.Dyesand Pigments,2017,136,782～790)所述方法制备PN：氮气保护下4-溴-1，8-萘酐与双(2-吡啶基甲基)胺在2-甲氧基乙醇中反应得到化合物PN。
酰胺-胺化合物M按文献方法制备。(Huanren Cheng,Ying Qian*.Synthesis andintramolecular FRET of perylenediimide-naphthalimide dendrons.Dyes andPigment,2015,112,317～326，文献中化合物编号为AN-Boc)。
氮气保护下将0.68g～2.04g化合物M和1.45g～4.35g化合物PN溶于100mL～150mL无水乙醇中，再加入1mL～3mL三乙胺，磁力搅拌下回流反应36h～48h，色谱柱提纯得到化合物A；将0.40g～1.20g化合物A溶于50mL～120mL无水甲醇中，滴加2mL～5mL浓盐酸，升温至50℃～60℃，磁力搅拌下反应24h～36h，旋蒸除去溶剂得到化合物B，将化合物B溶于30mL～70mL无水乙醇中，滴加溶有0.16g～0.48g PN的20mL～50mL无水乙醇，磁力搅拌下加入三乙胺调节溶液的pH值为8，回流反应36h～48h，得到化合物C，再经过减压蒸馏、柱色谱提纯、重结晶得到所述PDPN，总收率为20～25％。
PDPN的合成路线如下：
获得的化合物结构式为：
分析所得PDPN：
核磁共振氢谱1H NMR(300MHz，CDCl3):δ8.61(s，2H)，8.47(s，6H),8.21(s，3H)，8.03(s，6H)，7.53(t，J＝7.1Hz，6H)，7.42(s，3H)，7.28(t，J＝7.1Hz，6H)，7.04(m，9H)，4.59(s，12H)，4.02(s,4H)，3.36(s，8H)，3.01(s，4H)，2.57(s，4H)。
核磁共振氢谱13C NMR(CDCl3，ppm):δ171.7，164.7，164.1，157.1，154.0，149.4，136.7，132.1，131.1，130.5，130.0，126.3，125.7，122.8，122.4，122.4，117.3，115.8，59.6，49.9，39.5。
将实施例1制备的PDPN进行实施例2～5的试验，具体数据和分析如下：
实施例2：PDPN的固体态荧光及在水溶液中的聚集诱导荧光发射
图1为PDPN的固体荧光光谱。暗室中荧光化合物PDPN的固体粉末在紫外灯下发出鲜艳的黄色荧光，PDPN的固态最大荧光发射波长为548nm；固态PDPN的CIE荧光色坐标为(0.33，0.44)；PDPN在含水量10％～70％的水/有机混合溶剂中荧光较强，最大荧光发射波长位于526nm附近。
多吡啶萘酰亚胺荧光树形分子PDPN具有很强的聚集诱导发光特性，可作为聚集诱导发光材料，具有极其重要的应用价值。
实施例3 PDPN负载的水溶性二氧化硅纳米微球的荧光性质
保持0℃，在超声反应器中将0.44g二(2-乙基己基)琥珀酸磺酸钠溶于20mL去离子水中，搅拌下加入0.8mL正丁醇，缓慢滴加溶有15mM PDPN的30μL DMF溶液。滴加完毕后继续超声5min，加入0.2mL乙烯基三乙氧基硅烷，室温下搅拌8h，接着滴加15μL 3-氨基丙基三乙氧基硅烷后室温下搅拌36h。反应结束后用截留分子量为12-14kDa的纤维素透析膜在去离子水中透析72h，除去未包裹的染料及过量的活性剂和溶剂，再用0.45μM的水性过滤膜进行过滤，得到PDPN负载的水溶性二氧化硅荧光纳米微球，在5℃下保存使用。
图2为PDPN负载的二氧化硅荧光纳米微球在纯水中的荧光光谱，发射绿色荧光，荧光很强，最大发射峰位于511nm。
图3为PDPN负载的二氧化硅荧光纳米微球的TEM透射电镜照片。二氧化硅纳米粒子PDPN/SiO2呈球状分布，且分散均匀，负载PDPN的二氧化硅荧光纳米粒子易溶于水中，表面富含大量活性氨基，易于修饰，生物相容性好，荧光性质优良，可用于水溶液中的生物荧光分析、药物高通量筛选等生命科学领域。
实施例4 PDPN用于非治疗和诊断目的的细胞成像
肺癌细胞A-549在含有10％胎牛血清(FBS)、1％青霉素、1％两性霉素B的DMEM培养液中培养。成像之前，细胞在24孔板中培养24h。然后在37℃、5％CO2条件下，将PDPN以1.3×10-6g/L的浓度加入到培养液中共同培养4h，再用适量的PBS缓冲液洗涤多次除去多余的染料。将PDPN与肺癌细胞A-549共同孵化后在激光共聚焦荧光显微镜下观察肺癌细胞A-549细胞成像照片。附图4为肺癌细胞A-549与PDPN共同孵化后的激光共聚焦荧光成像照片。在肺癌细胞A-549中加入PDPN共同孵化后，绿光染料进入A-549肺癌细胞内部，在绿光区域清晰成像。PDPN可作为性能优良的荧光染料用于非治疗和诊断目的的肿瘤细胞成像。PDPN在生物细胞环境中具有良好的活性、耐光性及生物相容性，可以作为定位和追踪细胞的生物荧光探针。
实施例5 PDPN对pH的灵敏响应
图5为PDPN的荧光强度在不同pH下的变化趋势图。
PDPN的荧光强度随pH值逐渐增小而明显增强。表明PDPN可作为灵敏的pH荧光探针。
本发明的PDPN是由酰胺-胺中心核连接多个双吡啶甲基氨基萘酰亚胺荧光团，优化组合得到，具有优良的聚集诱导性能，可用于水溶性荧光纳米微球的制备，可作为性能优异的荧光染料用于肿瘤细胞的非治疗和诊断目的的荧光成像，该树形分子中多个吡啶甲基氨基萘酰亚胺荧光团具有非键合的超分子相互作用，可作为pH荧光探针，在荧光探针、荧光传感器、生物荧光标记等领域具有重要的应用价值。
以上所述仅是本发明的优选实施方式，应当指出：对于本技术领域的技术人员来说，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，这些改进和润饰也应视为本发明的保护范围。
Claims (8)
1.一种多吡啶萘酰亚胺聚集诱导荧光树形分子，其特征在于：该分子结构式如下：
2.一种如权利要求1所述的多吡啶萘酰亚胺荧光树形分子的制备方法，其特征在于：该方法包括如下步骤：
1)4-双(2-吡啶甲基)氨基-1，8-萘二甲酸酐PN与酰胺-胺化合物M在无水乙醇中，经三乙胺催化进行酰胺化反应，得到化合物A；
2)化合物A在无水甲醇中经盐酸催化脱保护后，得到化合物B；
3)化合物B在无水乙醇中，经三乙胺催化下与4-双(2-吡啶甲基)氨基-1，8-萘二甲酸酐PN进行酰胺化缩合反应，得到化合物C，之后经过减压蒸馏、柱色谱提纯、重结晶得到所述的多吡啶萘酰亚胺荧光树形分子，具体反应式如下：
。
3.如权利要求2所述的一种多吡啶萘酰亚胺荧光树形分子的制备方法，其特征在于：步骤1)所述的酰胺化反应的时长为36～48h。
4.如权利要求2所述的一种多吡啶萘酰亚胺荧光树形分子的制备方法，其特征在于：步骤3)所述的酰胺化缩合反应的时长为36～48h。
5.一种如权利要求1所述的多吡啶萘酰亚胺树形分子的应用，其特征在于：该分子应用于聚集诱导发光材料。
6.一种如权利要求1所述的多吡啶萘酰亚胺树形分子的应用，其特征在于：该分子应用于制备水溶性荧光纳米微球。
7.一种如权利要求1所述的多吡啶萘酰亚胺树形分子的应用，其特征在于：该分子作为荧光染料应用于肿瘤细胞的非治疗和诊断目的的成像方面。
8.一种如权利要求1所述的多吡啶萘酰亚胺树形分子的应用，其特征在于：该分子应用于pH荧光探针。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710023290.5A CN106831719B (zh) | 2017-01-12 | 2017-01-12 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710023290.5A CN106831719B (zh) | 2017-01-12 | 2017-01-12 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106831719A true CN106831719A (zh) | 2017-06-13 |
| CN106831719B CN106831719B (zh) | 2019-03-29 |
Family
ID=59123453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710023290.5A Active CN106831719B (zh) | 2017-01-12 | 2017-01-12 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106831719B (zh) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106831719B (zh) * | 2017-01-12 | 2019-03-29 | 东南大学 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
| CN113087702A (zh) * | 2021-03-29 | 2021-07-09 | 苏州大学 | 一种多功能过氯乙烯衍生物及其制备方法与应用 |
| CN115737914A (zh) * | 2022-11-25 | 2023-03-07 | 杭州矩正医疗科技有限公司 | 一种具有血管修复功能的感光材料制备方法 |
| CN115920139A (zh) * | 2022-11-25 | 2023-04-07 | 杭州矩正医疗科技有限公司 | 一种光动力球囊导管系统 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103408493A (zh) * | 2013-07-05 | 2013-11-27 | 东南大学 | 一种多臂萘酰亚胺荧光分子及其制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106831719B (zh) * | 2017-01-12 | 2019-03-29 | 东南大学 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
-
2017
- 2017-01-12 CN CN201710023290.5A patent/CN106831719B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103408493A (zh) * | 2013-07-05 | 2013-11-27 | 东南大学 | 一种多臂萘酰亚胺荧光分子及其制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| 罗晓燕等: ""多臂萘酰亚胺树枝分子的合成和荧光性质"", 《有机化学》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106831719B (zh) * | 2017-01-12 | 2019-03-29 | 东南大学 | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 |
| CN113087702A (zh) * | 2021-03-29 | 2021-07-09 | 苏州大学 | 一种多功能过氯乙烯衍生物及其制备方法与应用 |
| CN113087702B (zh) * | 2021-03-29 | 2022-07-12 | 苏州大学 | 一种多功能过氯乙烯衍生物及其制备方法与应用 |
| CN115737914A (zh) * | 2022-11-25 | 2023-03-07 | 杭州矩正医疗科技有限公司 | 一种具有血管修复功能的感光材料制备方法 |
| CN115920139A (zh) * | 2022-11-25 | 2023-04-07 | 杭州矩正医疗科技有限公司 | 一种光动力球囊导管系统 |
| CN115737914B (zh) * | 2022-11-25 | 2024-02-06 | 杭州矩正医疗科技有限公司 | 一种具有血管修复功能的感光材料制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106831719B (zh) | 2019-03-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106831719B (zh) | 一种多吡啶萘酰亚胺荧光树形分子及其制备方法和应用 | |
| CN106674028B (zh) | 一种苄叉茚二酮类化合物及其制备与在脂滴特异性成像中的应用 | |
| CN111995580B (zh) | 四苯乙烯并咪唑环结构的荧光染料及其应用 | |
| CN110358535B (zh) | 基于内滤效应检测硫化氢及活细胞内硫化氢成像的荧光碳点纳米探针及其使用方法 | |
| WO2019057196A1 (en) | FLUORESCENT COMPOUNDS FOR IMAGING LIPID DROPLETS AND IMAGE-GUIDED PHOTODYNAMIC THERAPY | |
| CN103254892B (zh) | 一种固态宽带蓝光发射有机发光材料及其制备方法 | |
| CN105440065B (zh) | 一种萘酰亚胺‑氟硼二吡咯荧光分子np‑bodipy及其制备方法和应用 | |
| CN114574196B (zh) | 一种高荧光量子产率的碳量子点制备方法及应用 | |
| Ma et al. | Comparation of multiple terminal functional groups dendrimer silicon (IV) phthalocyanines: Photoinduced electron/energy transfer and electrochemical properties | |
| CN103773060B (zh) | 有机荧光染料分子及其合成方法和应用 | |
| CN103409134B (zh) | 一种双荧光发射有机发光材料的制备方法 | |
| Zhu et al. | Rare earth upconversion luminescent composite based on energy transfer for specific and sensitive detection of cysteine | |
| CN105837568B (zh) | 一种芴基β‑咔啉类化合物，其作为有机发光材料和聚集诱导荧光增强材料的应用及制备方法 | |
| CN109251746A (zh) | 蒽环桥联双核钌配合物荧光探针的制备及其应用 | |
| Han et al. | A diphenylacrylonitrile conjugated porphyrin with near-infrared emission by AIE–FRET | |
| CN112218855B (zh) | Nir-ii发射性发光体 | |
| Ma et al. | Interfacial self-assembly of bipyridyl-functionalized nanoSiO2-BPy@ Ln (β-diketone) n composites and their luminescent properties | |
| CN108558834A (zh) | 一种哒嗪酮基三色荧光发射有机发光材料及其应用 | |
| CN115490677A (zh) | 一种可见光长波长活化的光开关分子及其合成方法和应用 | |
| CN112391047B (zh) | 一种温度刺激响应性苝二酰亚胺超分子荧光凝胶及制备方法与应用 | |
| CN113501836A (zh) | 一种星型bodipy近红外荧光染料及其制备方法 | |
| CN114479838B (zh) | 一种基于柱芳烃的光捕获体系及其制备方法和应用 | |
| CN104761578A (zh) | 基于铑四苯基卟啉-氮杂氟硼二吡咯近红外吸收磷光材料及其制法和用途 | |
| CN113329997A (zh) | 用于活细胞和深部组织中细胞器成像的光稳定的荧光化合物 | |
| CN108558739A (zh) | 一类基于萘并茚芴高双光子吸收的小分子材料及其制备方法 |
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 |