CN112457335A - 基于氟硼二吡咯结构有机染料、其合成方法及其应用 - Google Patents
基于氟硼二吡咯结构有机染料、其合成方法及其应用 Download PDFInfo
- Publication number
- CN112457335A CN112457335A CN202011239521.4A CN202011239521A CN112457335A CN 112457335 A CN112457335 A CN 112457335A CN 202011239521 A CN202011239521 A CN 202011239521A CN 112457335 A CN112457335 A CN 112457335A
- Authority
- CN
- China
- Prior art keywords
- organic dye
- compound
- bodipy structure
- hydrogen sulfide
- bodipy
- 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
- 238000010189 synthetic method Methods 0.000 title abstract description 5
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000001514 detection method Methods 0.000 claims abstract description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- 229940125782 compound 2 Drugs 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 229940125904 compound 1 Drugs 0.000 claims description 9
- 229940126214 compound 3 Drugs 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 230000002194 synthesizing effect Effects 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- SSFSNKZUKDBPIT-UHFFFAOYSA-N 2,4-dinitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C([N+]([O-])=O)=C1 SSFSNKZUKDBPIT-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- DDQPOYVWHPDXOX-UHFFFAOYSA-N 2,3-dinitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1[N+]([O-])=O DDQPOYVWHPDXOX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000011246 intracellular protein detection Methods 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 abstract description 5
- -1 2, 4-dinitrobenzenesulfonyl Chemical group 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract 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 abstract description 2
- 239000000975 dye Substances 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- 239000000523 sample Substances 0.000 description 9
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 8
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-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
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 229960003180 glutathione Drugs 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NQRKYASMKDDGHT-UHFFFAOYSA-N (aminooxy)acetic acid Chemical compound NOCC(O)=O NQRKYASMKDDGHT-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 102000020018 Cystathionine gamma-Lyase Human genes 0.000 description 2
- 108010045283 Cystathionine gamma-lyase Proteins 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 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- WDCYWAQPCXBPJA-UHFFFAOYSA-N 1,3-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC([N+]([O-])=O)=C1 WDCYWAQPCXBPJA-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- OJOLFAIGOXZBCI-UHFFFAOYSA-N 3-mercaptopyruvic acid Chemical compound OC(=O)C(=O)CS OJOLFAIGOXZBCI-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 102100034976 Cystathionine beta-synthase Human genes 0.000 description 1
- 108010073644 Cystathionine beta-synthase Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 240000006829 Ficus sundaica Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000840 electrochemical analysis Methods 0.000 description 1
- 230000009483 enzymatic pathway Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000979 synthetic dye Substances 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
-
- 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
-
- 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"
-
- 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
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—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
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1014—Carbocyclic 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
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
- C09K2211/1055—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms with other heteroatoms
-
- 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"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E10/00—Energy generation through renewable energy sources
- Y02E10/50—Photovoltaic [PV] energy
- Y02E10/542—Dye sensitized solar cells
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
本发明属于有机染料化合物及领域，具体涉及一种基于氟硼二吡咯结构有机染料、其合成方法及其应用。本发明以四苯基乙烯为电子供体，氟硼二吡咯(BODIPY)为电子受体，以2,4‑二硝基苯磺酰基为硫化氢的反应位点合成了一类新型的基于氟硼二吡咯结构有机染料，该有机染料为本发明首次合成，原料易得，过程简单，可产业化。且该有机染料对硫化氢的检测具有高选择性和高灵敏度，能够实现对硫化氢的快速检测，并伴随有荧光开启的现象，在环境硫化氢的检测和生物医学领域硫化氢信号分子的检测具有广泛的价值。
Description
技术领域
本发明属于有机染料化合物及小分子荧光探针领域，具体涉及一种基于氟硼二吡咯结构有机染料、其合成方法及其应用。
背景技术
硫化氢(H2S)被认为是生物体内继一氧化氮和一氧化碳之后的第三种气体递质。细胞内硫化氢主要是由L-半胱氨酸(Cys)通过独特的酶促途径生成，这些酶包括胱硫醚β-合成酶(CBS)，胱硫醚γ-裂合酶(CSE)和3-巯基丙酮酸硫转移酶(3-MST)。硫化氢可以在生理水平上调节细胞内的氧化还原状态和基本的信号传导过程。细胞中异常的硫化氢表达水平会诱发多种疾病，如肝硬化，癌症，阿尔茨海默症等。
传统的硫化氢检测方法主要有电化学分析法、比色法、色谱分析法等。这些方法操作流程相对繁琐，而且对样品预处理复杂容易损坏样品。荧光探针检测法相比于传统的硫化氢检测方法具有选择性好，灵敏度高，而且对样品破坏性小等优点。当然，在生物体内，硫化氢具有分布广，浓度低等特征。因此如何准确检测生物体内内源性硫化氢仍然面临着巨大的挑战。荧光探针的设计和合成可以采用模块化策略，可以利用硫化氢的化学性质构建合适的硫化氢响应基团再结合上高效的荧光团。目前，已经报道了一些有机小分子荧光探针用于硫化氢的分析检测，但是通常存在着响应时间长，易受生物硫醇干扰等缺点。
氟硼二吡咯结构有机染料在进入21世纪之后，由于其优异的光物理性能而受到科学家们广泛关注。氟硼二吡咯结构染料具有以下几个方面的优势：高摩尔消光系数，高荧光量子产率，高光热和化学稳定性，较窄的荧光光谱峰宽等。有优良荧光性能的氟硼二吡咯结构染料具备了作为高性能荧光团的潜力。
发明内容
本发明的目的是为了克服现有技术存在的缺点和不足，而提供一种基于氟硼二吡咯结构有机染料、其合成方法及其应用。
本发明的第一方面，提供一种基于氟硼二吡咯结构有机染料，该有机染料的结构通式为：
其中：R为H、卤素、C1～C20的直链烷氧基、C1～C20的支链烷氧基、C1～C20的二烷基氨基。
优选地，其中R为H。
本发明的第二方面，提供如上述的基于氟硼二吡咯结构有机染料的合成方法，包括以下步骤：
(1)化合物1与化合物3反应得到化合物2；
所述化合物1的结构式为：
所述化合物3的结构式为：
所述化合物2的结构式为：
(2)将化合物2与二硝基苯磺酰氯反应，得到如权利要求1或2所述的基于氟硼二吡咯结构有机染料。
优选地，步骤(1)中，化合物1与化合物3溶解在THF中，加入K2CO3水溶液和催化剂，在惰性气体保护下加热回流反应，待反应结束后，分离提纯得到化合物2。
优选地，其中，化合物1、化合物3、K2CO3、催化剂的摩尔比为1:2.2:6:0.05。
优选地，所述催化剂为Pd(PPh3)4。
优选地，步骤(2)中，以无水二氯甲烷为溶剂，加入化合物2、三乙胺，在惰性气体保护下，冰浴条件下搅拌，然后滴加含有2,4-二硝基苯磺酰氯的二氯甲烷溶液，滴加完毕后，在常温下反应，待反应结束后，分离提纯得到如权利要求1或2所述的基于氟硼二吡咯结构有机染料。
本发明的第三方面，提供如上述的基于氟硼二吡咯结构有机染料用于制备硫化氢检测试剂的应用。
本发明的第四方面，提供如上述的基于氟硼二吡咯结构有机染料用于硫化氢检测的应用，其特征在于：所述的基于氟硼二吡咯结构有机染料与H2S作用之后，出现荧光“turn-on”现象。
本发明的第五方面，提供如上述的基于氟硼二吡咯结构有机染料用于细胞内硫化氢检测的应用。
本发明的有益效果体现在：
(1)本发明以四苯基乙烯为电子供体，氟硼二吡咯(BODIPY)为电子受体，以2,4-二硝基苯磺酰基为硫化氢的反应位点合成了一类新型的基于氟硼二吡咯结构有机染料，该有机染料为本发明首次合成，原料易得，过程简单，可产业化，具有较强的商业价值。
(2)本发明提供的有机染料在THF/PBS(v/v＝1/1，pH＝7.4)溶液中与硫化氢作用之后，紫外可见吸收光谱和荧光发射光谱都发生了明显的变化，因此该类有机染料可以实现对硫化氢的可视化检测。
(3)本发明提供的有机染料对硫化氢的检测具有良好的选择性和抗干扰能力，F-，Cl-，Br-，I-，NO3 -，CO3 2-，PO4 3-，S2O5-，SO3 2-，HSO3 -，S2O5 -，S2O8 2-，H2O2，丙氨酸(Ala)，脯氨酸(Pro)，谷氨酸(Glu)，谷氨酰胺(Gln)，甲硫氨酸(Met)，精氨酸(Arg)，丝氨酸(Ser)，苏氨酸(Thr)，天冬酰胺(Asn)，组氨酸(His)，半胱氨酸(Cys)，高半胱氨酸(Hcy)，谷胱甘肽(GSH)等离子和氨基酸都不会对该有机染料对硫化氢的检测造成干扰。
(4)本发明提供的有机染料对硫化氢的检测具有很高的灵敏度，达到了纳摩尔级别，这为细胞内源性硫化氢检测实验提供了支持。
(5)本发明提供的有机染料对硫化氢的检测是基于硫化氢的亲核性，硫化氢对有机染料发生的亲核取代反应。
(6)本发明提供的有机染料能够快速的进入细胞，并实现结肠癌细胞中内源性硫化氢的检测。
综上所述，本发明提供一种新的基于氟硼二吡咯结构有机染料，该有机小分子荧光探针制备简单，对硫化氢的检测具有高选择性和高灵敏度，能够实现对硫化氢的快速检测，并伴随有荧光开启的现象，在环境硫化氢的检测和生物医学领域硫化氢信号分子的检测具有广泛的价值。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，根据这些附图获得其他的附图仍属于本发明的范畴。
图1为实施例1的合成路线图；
图2(a)为实施例1中所合成的染料在THF/PBS缓冲液(v/v＝1/1,pH＝7.4)溶剂中(染料浓度:10μM)与H2S(150μM)反应前后的紫外可见吸收光谱图，图2(b)为染料在THF/PBS缓冲液(v/v＝1/1,pH＝7.4)溶剂中(染料浓度:10μM)与H2S(150μM)反应前后的荧光发射光谱图；
图3(a)为实施例1中所合成的染料在THF/PBS缓冲液(v/v＝1/1,pH＝7.4)溶剂中(浓度:10μM)与测试样品(150μM)反应后的荧光强度柱状图，图3(b)为染料在THF/PBS缓冲液(v/v＝1/1,pH＝7.4)溶剂中(浓度:10μM)与H2S(150μM)和其他测试样品共同存在反应后的荧光强度柱状图；测试样品：1.Free,2.Br-,3.CO3 2-,4.F-,5.I-,6.Cl-,7.SO3 2-,8.HSO3 -,9.S2O5 -,10.S2O8 2-,11.NO3 -,12.PO4 3-,13.H2O2,14.Ala,15.Pro,16.Gln,17.Glu,18.Met,19.Arg,20.Ser,21.Thr,22.Asn,23.His,24.Cys,25.GSH,26.Hcy.27.H2S；
图4(a)为实施例1中合成的染料(10μM)与不同浓度H2S(5,10,15,20,25,30,35,40,45,50,60,70,80,90,100,150,200,300μM)反应后的荧光光谱变化图，图4(b)为实施例1中合成染料(10μM)的荧光强度与H2S浓度(1-7μM)的线性关系图；
图5为实施例1中合成的染料在氘代DMSO中滴加不同当量H2S的核磁氢谱变化图；
图6为实施例1中合成的染料在结肠癌细胞(HCT116)中与内源性H2S反应后的荧光共聚焦图，(A1,A4,A7)HCT116细胞用SAM(3mM)培养1h，再加DT(10μM)培养1h；(A2,A5,A8)HCT116细胞加DT(10μM)培养1h；(A3,A6,A9)HCT116细胞用AOAA(1mM)培养1h，再加DT(10μM)培养1h；A1-A3是A4-A6对应的DAPI图；A7-A9是A4-A6对应的明亮视野图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将结合附图对本发明作进一步地详细描述。
实施例1
基于氟硼二吡咯结构有机染料DT的合成
(1)化合物2的合成
在氩气的保护下，在一个50mL的二口圆底烧瓶中加入498mg(1.0mmol)化合物1，1008mg(2.2mmol)1-(4-苯硼酸频哪醇酯)-1,2,2-三苯乙烯，3mL K2CO3水溶液(2M)，20mL四氢呋喃溶剂，最后再加入115mg(0.1mmol)Pd(PPh3)4催化剂。反应液温度升至70℃并搅拌反应16h。待反应液冷却至室温后加入30mL蒸馏水，并用二氯甲烷萃取三次。得到的有机层用无水MgSO4干燥后用旋蒸仪除去溶剂，粗产物用硅胶柱层析进行分离提纯，以石油醚：二氯甲烷(1:3)为流动相，得到(0.67g)紫色固体化合物2，产率为67％。1H NMR(400MHz,CDCl3)δ7.18–7.15(m,2H),7.14–6.99(m,34H),6.96–6.94(m,2H),6.88–6.86(m,4H),2.48(s,6H),1.32(s,6H).HRMS(ESI,m/z):[M+Na]+cacld for C71H55BF2N2NaO:1023.4268,found:1023.4298.
(2)有机染料DT的合成
在氩气的保护下，在一个50mL的二口圆底烧瓶中，加入500mg(0.5mmol)化合物2，15mL二氯甲烷和0.1mL三乙胺。反应混合液在0℃下搅拌反应5分钟后，往反应液中缓慢滴加400mg(1.5mmol)2,4-二硝基苯环酰氯的二氯甲烷溶液(10mL)，滴加完毕后继续在常温下搅拌反应2h。反应结束后，往反应液中加入30mL蒸馏水，用二氯甲烷萃取三次，合并的有机相用无水MgSO4干燥。用旋蒸仪除去有机溶剂，粗产物用硅胶柱层析进行分离提纯，以石油醚：二氯甲烷(1:3)为流动相，得到(0.50g)紫色固体染料DT，产率为81％。1H NMR(400MHz,CDCl3)δ8.68(d,J＝2.0Hz,1H),8.46–8.43(m,1H),8.21–8.14(m,1H),7.39(s,4H),7.14–7.01(m,34H),6.85(d,J＝8.2Hz,4H),2.48(s,6H),1.21(s,6H).HRMS(ESI,m/z):[M+Na]+cacld for C77H57BF2N4NaO7S:1253.3901,found:1253.3975.
实施例2
对实施例1的有机染料DT进行了与硫化氢响应后的紫外和荧光发射光谱测试，如图2所示。DT的最大吸收波长在540nm，在与H2S作用之后，染料的最大吸收峰蓝移到了534nm。而染料DT与H2S反应前后的荧光强度则发生了明显的变化。染料DT在不加入H2S之前的荧光发射信号很弱，而在加入H2S之后，染料探针溶液有明显的荧光“turn-on”现象，在579nm出现了很强的荧光信号峰。这说明在紫外灯下，我们可以通过裸眼观测染料DT对H2S的检测结果。
实施例3
对实施例1的有机染料DT进行了选择性实验。如图3a所示，除了生物硫醇(Cys、Hcy、GSH)与染料DT作用后有微小的荧光强度变化以外，其他氨基酸和代表性的阴离子的加入都不会使染料DT的荧光发射出现明显的变化。然而H2S的加入可以让染料DT的荧光发生明显“turn-on”现象变化。此外，如图3b所示，在其他竞争性样品存在的情况下，H2S仍会引发染料探针DT出现与图3a相似的荧光响应现象。从选择性实验中可以说明有机染料探针DT对H2S具有很好的选择性。
实施例4
对实施例1的有机染料DT进行了荧光滴定实验，如图4所示。染料DT自身的荧光很弱，随着H2S的加入，染料在579nm处的荧光发射强度逐渐增强。图4b为染料DT在H2S浓度为1-7μM范围内的荧光滴定实验，通过线性关系拟合直线并计算得到染料DT对H2S的检测限为6.39nM。这结果说明染料DT对H2S具有很高的灵敏度。
实施例5
对实施例1的有机染料DT进行了反应机理的核磁氢谱滴定实验，如图5所示。在9.11、8.50、8.19ppm处的峰分别对应于DT分子中二硝基苯的H1、H2和H3。在7.53、7.40ppm处的信号属于与BODIPY上连接的苯环上H4、H5。先后滴加0.33、0.66和1.00当量的硫化氢溶液后，探针的化学位移发生了明显的变化。与此同时，在9.88ppm处出现了一个新的峰是属于化合物2的羟基氢。这说明染料DT与硫化氢的作用是由于硫化氢的亲核进攻反应引起的，然后生成了化合物2。
实施例6
对实施例1的有机染料DT对结肠癌细胞(HCT116)中内源性H2S进行了成像检测，如图6所示。内源性H2S与CBS表达有关。SAM作为CBS的激活剂，可诱导内源性H2S水平升高。相反，AOAA通过抑制CBS表达来降低内源性H2S水平。如图6-A5所示，用DT孵育的HCT116细胞显示出明显的绿色荧光，而用SAM和DT一起孵育的HCT116细胞则显示出更强的荧光。该实验说明有机染料探针DT能够点亮并检测结肠癌细胞中的硫化氢。
以上所揭露的仅为本发明较佳实施例而已，当然不能以此来限定本发明之权利范围，因此依本发明权利要求所作的等同变化，仍属本发明所涵盖的范围。
Claims (10)
1.一种基于氟硼二吡咯结构有机染料，其特征在于：该有机染料的结构通式为：
其中：R为H、卤素、C1～C20的直链烷氧基、C1～C20的支链烷氧基、C1～C20的二烷基氨基。
2.根据权利要求1所述的基于氟硼二吡咯结构有机染料，其特征在于：其中R为H。
3.如权利要求1或2所述的基于氟硼二吡咯结构有机染料的合成方法，其特征在于包括以下步骤：
(1)化合物1与化合物3反应得到化合物2；
所述化合物1的结构式为：
所述化合物3的结构式为：
所述化合物2的结构式为：
(2)将化合物2与二硝基苯磺酰氯反应，得到如权利要求1或2所述的基于氟硼二吡咯结构有机染料。
4.根据权利要求3所述的基于氟硼二吡咯结构有机染料的合成方法，其特征在于：
步骤(1)中，化合物1与化合物3溶解在THF中，加入K2CO3水溶液和催化剂，在惰性气体保护下加热回流反应，待反应结束后，分离提纯得到化合物2。
5.根据权利要求4所述的于氟硼二吡咯结构有机染料的合成方法，其特征在于：化合物1、化合物3、K2CO3、催化剂的摩尔比为1:2.2:6:0.05。
6.根据权利要求4所述的于氟硼二吡咯结构有机染料的合成方法，其特征在于：所述催化剂为Pd(PPh3)4。
7.根据权利要求3所述的基于氟硼二吡咯结构有机染料的合成方法，其特征在于：
步骤(2)中，以无水二氯甲烷为溶剂，加入化合物2、三乙胺，在惰性气体保护下，冰浴条件下搅拌，然后滴加含有2,4-二硝基苯磺酰氯的二氯甲烷溶液，滴加完毕后，在常温下反应，待反应结束后，分离提纯得到如权利要求1或2所述的基于氟硼二吡咯结构有机染料。
8.如权利要求1或2所述的基于氟硼二吡咯结构有机染料用于制备硫化氢检测试剂的应用。
9.如权利要求1或2所述的基于氟硼二吡咯结构有机染料用于硫化氢检测的应用，其特征在于：所述的基于氟硼二吡咯结构有机染料与H2S作用之后，出现荧光开启现象。
10.如权利要求1或2所述的基于氟硼二吡咯结构有机染料用于细胞内硫化氢检测的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011239521.4A CN112457335B (zh) | 2020-11-09 | 2020-11-09 | 基于氟硼二吡咯结构有机染料、其合成方法及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011239521.4A CN112457335B (zh) | 2020-11-09 | 2020-11-09 | 基于氟硼二吡咯结构有机染料、其合成方法及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112457335A true CN112457335A (zh) | 2021-03-09 |
| CN112457335B CN112457335B (zh) | 2023-05-26 |
Family
ID=74825833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011239521.4A Active CN112457335B (zh) | 2020-11-09 | 2020-11-09 | 基于氟硼二吡咯结构有机染料、其合成方法及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112457335B (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110092863A (zh) * | 2019-05-15 | 2019-08-06 | 浙江理工大学 | 一种氨基和多肽修饰的aie聚合物纳米粒子的制备方法 |
| CN110128583A (zh) * | 2019-03-06 | 2019-08-16 | 浙江理工大学 | 一种氨基和多肽修饰的aie聚合物纳米粒子的制备方法 |
| CN111233876A (zh) * | 2020-02-27 | 2020-06-05 | 湖南科技大学 | 一种快速检测硫化氢的荧光探针及其制备方法和应用 |
-
2020
- 2020-11-09 CN CN202011239521.4A patent/CN112457335B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128583A (zh) * | 2019-03-06 | 2019-08-16 | 浙江理工大学 | 一种氨基和多肽修饰的aie聚合物纳米粒子的制备方法 |
| CN110092863A (zh) * | 2019-05-15 | 2019-08-06 | 浙江理工大学 | 一种氨基和多肽修饰的aie聚合物纳米粒子的制备方法 |
| CN111233876A (zh) * | 2020-02-27 | 2020-06-05 | 湖南科技大学 | 一种快速检测硫化氢的荧光探针及其制备方法和应用 |
Non-Patent Citations (2)
| Title |
|---|
| LI, QINGYUN ET AL.: "A NIR fluorescent probe for the detection and visualization of hydrogen sulfide in colorectal cancer cell", 《SENSORS AND ACTUATORS, B: CHEMICAL》 * |
| LI, ZHENSHENG ET AL.: "A tetraphenylethene-decorated BODIPY monomer/dimer with intense fluorescence in various matrixes", 《NEW JOURNAL OF CHEMISTRY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112457335B (zh) | 2023-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | A novel imidazo [1, 5-α] pyridine-based fluorescent probe with a large Stokes shift for imaging hydrogen sulfide | |
| CN110540837B (zh) | 一种过氧化氢近红外荧光探针的制备和应用 | |
| Wang et al. | A new mitochondria-targeting fluorescent probe for ratiometric detection of H2O2 in live cells | |
| Wang et al. | A novel p-aminophenylthio-and cyano-substituted BODIPY as a fluorescence turn-on probe for distinguishing cysteine and homocysteine from glutathione | |
| Maity et al. | A turn-on NIR fluorescence and colourimetric cyanine probe for monitoring the thiol content in serum and the glutathione reductase assisted glutathione redox process | |
| Zhao et al. | A novel “turn-on” mitochondria-targeting near-infrared fluorescent probe for H2S detection and in living cells imaging | |
| CN108129365B (zh) | 一种近红外检测半胱氨酸的荧光探针、其制备方法及应用 | |
| Yang et al. | A fluorescent dyad with large emission shift for discrimination of cysteine/homocysteine from glutathione and hydrogen sulfide and the application of bioimaging | |
| CN107602502B (zh) | 一种用于生物硫醇检测的esipt型荧光探针及应用 | |
| CN109867611B (zh) | 一种用于红酒和活体内硫化氢检测的水溶性双光子硫化氢荧光探针及其制备方法和应用 | |
| Chen et al. | A nitroso-based fluorogenic probe for rapid detection of hydrogen sulfide in living cells | |
| Chen et al. | A turn-on fluorescent probe for simultaneous sensing of cysteine/homocysteine and hydrogen sulfide and its bioimaging applications | |
| Liu et al. | A squaraine-based red emission off–on chemosensor for biothiols and its application in living cells imaging | |
| Qian et al. | 2-Vinylfuran substituted BODIPY H2S fluorescent turn on probe based on hydrolysis of furfural and nucleophilic addition of double bond | |
| Zhang et al. | Acryl-modified diazabenzo [ghi] perylene for fast discrimination of Cys from GSH and Hcy with high quantum yield | |
| CN110698401A (zh) | 一种检测生物硫醇新型荧光探针及其制备方法和应用 | |
| Zhang et al. | Development of a novel near-infrared fluorescence light-up probe with a large Stokes shift for sensing of cysteine in aqueous solution, living cells and zebrafish | |
| Lu et al. | Ultrafast deep-red emission fluorescent probe for highly selective imaging of endogenous cysteine in living cells and mice | |
| Mani et al. | Smart phone assisted quinoline-hemicyanine based fluorescent probe for the selective detection of glutathione and the application in living cells | |
| Huang et al. | Ratiometric and colorimetric detection of hydrogen sulfide with high selectivity and sensitivity using a novel FRET-based fluorescence probe | |
| Zhang et al. | Red emissive fluorescent probe for the rapid detection of selenocysteine | |
| Zhao et al. | A novel “turn-on” mitochondria-targeting near-infrared fluorescent probe for determination and bioimaging cellular hydrogen sulfide | |
| Chen et al. | A highly selective colorimetric and fluorescent probe for cysteine sensing: application in live cell imaging and test strips | |
| Hou et al. | A reversible turn-on fluorescent probe for quantitative imaging and dynamic monitoring of cellular glutathione | |
| Zhang et al. | Design, synthesis and characterization of a novel fluorescent probe for nitric oxide based on difluoroboradiaza-s-indacene fluorophore |
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 |