CN108864071A - A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications - Google Patents
A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications Download PDFInfo
- Publication number
- CN108864071A CN108864071A CN201810600223.XA CN201810600223A CN108864071A CN 108864071 A CN108864071 A CN 108864071A CN 201810600223 A CN201810600223 A CN 201810600223A CN 108864071 A CN108864071 A CN 108864071A
- Authority
- CN
- China
- Prior art keywords
- compound
- probe
- molar ratio
- added
- nitric oxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000523 sample Substances 0.000 title claims abstract description 90
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 230000004044 response Effects 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 17
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 claims abstract description 17
- 210000004556 brain Anatomy 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 30
- 230000015572 biosynthetic process Effects 0.000 claims description 29
- 238000003786 synthesis reaction Methods 0.000 claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- JEDHEMYZURJGRQ-UHFFFAOYSA-N 3-hexylthiophene Chemical compound CCCCCCC=1C=CSC=1 JEDHEMYZURJGRQ-UHFFFAOYSA-N 0.000 claims description 20
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical class C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 239000004698 Polyethylene Substances 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 15
- 229920000573 polyethylene Polymers 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 13
- 229940125898 compound 5 Drugs 0.000 claims description 13
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 12
- -1 4- hexyl Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 229940125782 compound 2 Drugs 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- FEOWHLLJXAECMU-UHFFFAOYSA-N 4,7-dibromo-2,1,3-benzothiadiazole Chemical class BrC1=CC=C(Br)C2=NSN=C12 FEOWHLLJXAECMU-UHFFFAOYSA-N 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 239000012264 purified product Substances 0.000 claims description 10
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 8
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- 229940126214 compound 3 Drugs 0.000 claims description 7
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 229910017604 nitric acid Inorganic materials 0.000 claims description 6
- 230000001376 precipitating effect Effects 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000004458 analytical method Methods 0.000 claims description 5
- 238000005660 chlorination reaction Methods 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 238000004090 dissolution Methods 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 5
- 235000003270 potassium fluoride Nutrition 0.000 claims description 5
- 239000011698 potassium fluoride Substances 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 229910000080 stannane Inorganic materials 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 230000001413 cellular effect Effects 0.000 claims description 3
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 claims description 3
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 1
- 239000000779 smoke Substances 0.000 claims 1
- 238000001514 detection method Methods 0.000 abstract description 13
- 208000018737 Parkinson disease Diseases 0.000 abstract description 6
- 230000035945 sensitivity Effects 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 4
- 230000036632 reaction speed Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000013399 early diagnosis Methods 0.000 abstract description 2
- 230000004962 physiological condition Effects 0.000 abstract 1
- 239000001963 growth medium Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 230000005284 excitation Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 210000003739 neck Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 5
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000007845 reactive nitrogen species Substances 0.000 description 4
- 239000003642 reactive oxygen metabolite Substances 0.000 description 4
- 239000013049 sediment Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 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 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000006862 quantum yield reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 0 CCC=C(c(c1n[s]nc1c(-c1cc(*)c[s]1)c1N)c1N)S Chemical compound CCC=C(c(c1n[s]nc1c(-c1cc(*)c[s]1)c1N)c1N)S 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 1
- AQGDXJQRVOCUQX-UHFFFAOYSA-N N.[S] Chemical compound N.[S] AQGDXJQRVOCUQX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 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
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000004427 diamine group Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K49/003—Thiazine 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"
-
- 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
- C09K2211/1051—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms with sulfur
-
- 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
- C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom
Abstract
The present invention relates to a kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications to belong to organic fluorescence probe field shown in structure such as formula (I).The present invention has designed and synthesized the near-infrared nitric oxide probe of a kind of quick response.There is near infrared emission after the probe and NO response.Experiment in vitro is studies have shown that probe and NO reaction speed are fast.At physiological condition (pH 7.4), probe steady, and to NO sensitivity with higher, selectivity and anti-interference.Bioexperiment can also be applied to the detection of NO level in PD cell and drosophila brain model studies have shown that probe can be applied not only to the detection of endogenous NO level in cell.These results indicate that probe specificity with higher, selectivity, stability, may be applied to the early diagnosis of Parkinson's disease in the future.
Description
Technical field
The present invention relates to nitric oxide near-infrared probe of a kind of quick response and preparation method thereof and biologic applications, belong to
Organic fluorescence probe field.
Background technique
Nitric oxide (Nitric Oxide, NO) be by nitric oxide synthetase (Nitric Oxide Synthetase,
NOS) the cell messenger molecule synthesized, it plays an important role in cardiovascular, nerve and immune system.The effect of NO is depended on
The distribution of NO concentration and time and space in cell micro-environment.Abnormal generate of NO has with the pathogenic process of many diseases
It closes, such as cancer, endothelial dysfunction and neurodegenerative disease.More and more researches show that NO is in common neurological
Key effect has been played in the pathogenesis of property disease-Parkinson's disease (Parkinson ' s disease, PD).But in organism
The method of NO detection is still to be improved.Currently, the main method of NO level is one oxidation of immunoblotting detection in detection PD
The expression quantity of nitrogen synzyme, this method cannot direct, NO in real-time monitoring living cells levels.Therefore, it designs a kind of real-time
The probe of NO level has great importance to effect of the research NO in PD in detection living cells.
NO fluorescence probe has many advantages, such as that high sensitivity, selectivity are high, spatial and temporal resolution is high, experiment is convenient, has been developed that
And it is applied to the imaging of NO in cell and organism, let us, which has function of the NO in cell and organism, more to be recognized
Know.There are mainly two types of different types for the NO fluorescence probe reported at present, and one is the exploitations of Nagano seminar based on adjacent benzene
The response type nitric oxide probe of diamine structures, another kind are that the metal ion complex one of Lippard seminar report aoxidizes
Nitrogen probe.In NO fluorescence probe, using o-phenylenediamine to capture group as NO is most common method.Its principle is adjacent benzene
Diamines adjusts Photo-induced electron transfer (PET) process as reaction site, and the fluorogen of probe is in quenching state up to it
It is reacted with NO, blocks PET process, fluorogen is made to restore fluorescence to reflect the level of NO.This type probes have high sensitivity,
PH is stable and can be used for the advantages that NO inside and outside organism is imaged.However, there is also some limitations for this type probes.Example
Such as, short excitation wavelength makes probe have the shortcomings that penetration depth is shallow, light injury is big and cell autofluorescence is strong.Based on o-dihydroxy ammon
The interference by oxidants such as glutathione is easy for the fluorescence probe of NO recognition group.And these NO fluorescence for having delivered
There is no a kind of detection for being further applied NO in Parkinson disease model in probe.
In order to solve problem above, it is necessary to develop a kind of novel nitric oxide probe.The present invention using o-phenylenediamine as
NO recognition group, design have synthesized the near-infrared nitric oxide probe of a kind of quick response.Have after the probe and NO response close
Infrared emission, therefore have many advantages, such as that tissue penetration is strong, light injury is weak and it is weak to be influenced by tissue autofluorescence, and after reaction
Fluorescence quantum yield significantly increases.Experiment in vitro is studies have shown that probe and NO reaction speed are fast.At biotic factor (pH 7.4)
Under, probe steady, and to NO sensitivity with higher and selectivity, not by the interference of other ions and amino acid.It is biological real
It tests studies have shown that probe is low to cytotoxicity, and can detecte the level of external source and endogenous NO in cell.Further by probe
Applied in PD cell model, the experimental results showed that probe can intuitively show that endogenous NO is horizontal in PD cell model.
In addition, the fluorescent emission after reacting in view of probe with NO is near infrared region, there are stronger tissue penetration, therefore we
Further by probe application in PD drosophila brain model, the experimental results showed that, probe can reflect out the level of NO in PD drosophila brain.
These results indicate that probe specificity with higher, selectivity, stability, may be applied to the morning of Parkinson's disease in the future
Phase diagnosis.
Summary of the invention
More than solving the problems, such as, it is high, special to provide a kind of sensitivity using o-phenylenediamine as NO acquirer by the present invention
Anisotropic near-infrared NO probe strong, reaction speed is fast, the probe not only can detecte the content of the intracorporal NO of biology, can also examine
Survey the content of NO in PD cell model and PD drosophila brain model.
To solve prior art problem, the technical scheme adopted by the invention is as follows：A kind of quick response it is nitric oxide production close
Infrared probe, the fluorescence probe are BT-NH fluorescence probe, and structure is as shown in I：
Further, o-phenylenediamine is introduced as NO acquirer, introduces the solubility that hexyl alkyl chain improves probe.
To solve prior art problem, the technical scheme adopted by the invention is as follows：A kind of quick response it is nitric oxide production close
The preparation and biologic applications of infrared probe, include the following steps：
Step 1：The synthesis of tributyl (the thio Fei Fen -2- base of 4- hexyl) stannane (1)
3- hexyl thiophene (2.50-10.00g) and the dry type tetrahydrofuran (50.00-200.00mL) of fresh distillation are placed in
In the mono- neck bottle of 250ml, in a nitrogen environment, after -78 DEG C are stirred 30 minutes, tributyltin chloride (8.16- is added dropwise
32.64mL in THF) stirring 2 hours.Then tributyl chlorination (5.08-20.30.00mL) is added.Mixture is placed in room
Temperature stirs 12 hours.After reaction, (50.00-200.00mL) is added in mixed liquor and is extracted with hexane.Organic layer nothing
Aqueous sodium persulfate is dry, and with solvent is removed in vacuo, obtains brown liquid compound 1.
Step 2：The synthesis of benzo [c] [1,2,5] thiadiazoles (2)
O-phenylenediamine (2.50-10.00g) is added into 1000 milliliters of two-neck bottles, and is dissolved in methylene chloride
In the mixed solution of (100.00-400.00mL) and triethylamine (9.35-37.40g), Asia is then slowly added dropwise by dropping funel
Chlorosulfuric acid (1.85-7.40mL), until flowing back 20 hours after solid is completely dissolved.Mixture removes solvent under low pressure, then plus
Enter polyethylene (150.00-600.00mL) dissolution.By mixed liquor filtering and collecting filter liquid, solvent is removed in a vacuum, obtains palm fibre
Color solid chemical compound 2.
Step 3：The synthesis of 4,7- dibromo benzo [c] [1,2,5] thiadiazoles (3)
Compound 2 (2.50-10.00g) is added in 500ml double-neck flask and is dissolved in hydrogen bromide (47%, 40.00-
In 160.00mL).Double necks will be slowly added to containing the hydrogen bromide (47%, 25.00-100.00mL) of bromine (8.80-35.20g)
In flask.After the entry to be completely, mixture is flowed back 6 hours, until forming orange solids precipitating.Object to be mixed is cooled to room temperature
Afterwards, it filters mixture and acquisition light yellow solid is washed with water.Solid is recrystallized with chloroform, obtains compound as white solid 3.
Step 4：The synthesis of bromo- 5-6- dinitro benzo [c] [1,2, the 5]-thiadiazoles (4) of 4-7- bis-
At 0 DEG C, double necks containing trifluoromethanesulfonic acid (15.30-61.20g) are added dropwise in nitric acid (1.25-5.00g)
In flask, after stir about 30 minutes, compound 3 (2.50-10.00g) is added in mixed acid in 10 minutes.At 50 DEG C
After being stirred overnight, when only showing a spot with thin-layered chromatography (TLC) analysis mixed liquor, pour the mixture into ice water, mistake
It after filter obtains sediment, is washed with water, and with ethyl alcohol recrystallization purified product.Obtain yellow solid compound 4.
Step 5：The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) -5,6- dinitro benzo [c] [1,2,5] thiadiazoles (5)
Compound 4 (1.00-4.00g) is first dissolved in tetrahydrofuran (10.00-40.00mL) and dimethyl carbonamidine
In the mixed liquor of (5.00-20.00mL), then in a nitrogen environment, by compound 1 (3.55-14.20g) and bi triphenyl phosphorus
Palladium chloride (0.02-0.10g) is added in solution.Mixture reacts overnight at 100 DEG C, and object to be mixed is cooled to room temperature
Afterwards, potassium fluoride (10.00-40.00mL) is added, after being filtered with Celite, collects filtrate and be concentrated.Product is through column chromatography (two
Chloromethanes:Polyethylene=1:10) it purifies, obtains orange solids compound 5.
Step 6：The conjunction of 4,7- bis- (4- hexyl thiophene -2- base) benzo [c] [1,2,5] thiadiazoles -5,6- diamines (BT-NH)
At
Under a nitrogen atmosphere, that compound 5 (0.50-2.00g) is dissolved in acetic acid (7.50-30.00mL) is inner, is then added
Iron (0.50-2.00g).It heats the mixture to 80 DEG C to react 6 hours, after object to be mixed is cooled to room temperature, be mentioned with ethyl acetate
Product is taken, and is washed with sodium hydrate aqueous solution.Solvent is removed under low pressure, chromatographs (ethyl acetate with column：Polyethylene=1：
10) purified product obtains yellow solid BT-NH.
The fluorescence probe is BT-NH fluorescence probe, improved as preparation method to be, step (1) the 3- hexyl
The molar ratio of thiophene and lithium diisopropylamine is 1：1.0-1：1.2, preferred molar ratio 1：1.0-1：1.1；3- hexyl thiophene
Molar ratio with tributyltin chloride is 1：1.0-1：1.1, preferred molar ratio 1：1.0-1：1.05.
Improved as preparation method to be, the molar ratio of step (2) o-phenylenediamine and thionyl chloride is 1：1.0-1：
1.3, preferred molar ratio 1：1.0-1：1.1.
Improved as preparation method to be, step (3) compound 2 and the molar ratio of bromine are 1：2.0-1：4.0, it is excellent
Selecting molar ratio is 1：2.5-1：3.0.
Improved as preparation method to be, step (4) compound 3 and the molar ratio of fuming nitric aicd are 1：2.0-1：
4.0, preferred molar ratio 1：3.0-1：4.0；Fuming nitric aicd and trifluoromethanesulfonic acid molar ratio are 1：3.0-1：4.0, preferably mole
Than being 1：3.0-1：3.5.
Improved as preparation method to be, step (5) compound 4 and the molar ratio of chemical combination 1 are 1：2.0-1：2.5
Preferred molar ratio is 1：2.1-1：2.2；The molar ratio of compound 4 and bi triphenyl phosphorus palladium chloride is 1：0.03-1：0.1, it is excellent
Selecting molar ratio is 1：0.03-1：0.05.
Improved as preparation method to be, step (6) is described, and the molar ratio of compound 5 and iron powder is 1：7.0-1：12.0,
Preferred molar ratio is 1：7.0-1：10.0.
Beneficial effect：
Fluorescence probe of the invention has the advantages that near infrared emission, therefore has that tissue penetration is strong, light injury is weak
The advantages that weak is influenced with by tissue autofluorescence, and fluorescence quantum yield significantly increases after reaction.Experiment in vitro is studies have shown that visit
Needle and NO reaction speed are fast.At biotic factor (pH 7.4), probe steady, and to NO sensitivity with higher and selection
Property, not by the interference of other 52 kinds of ions and amino acid.Bioexperiment is studies have shown that probe is low to cytotoxicity, and can examine
Survey the level of external source and endogenous NO in cell.It is real further by probe application in PD cell model and PD drosophila brain model
It tests the result shows that probe can intuitively show that endogenous NO is horizontal in PD model.These results indicate that the probe in the future can
It can apply to the early diagnosis of Parkinson's disease.
Detailed description of the invention
Fig. 1 is the hydrogen spectrum of compound 5.
Fig. 2 is the carbon spectrum of compound 5.
Fig. 3 is the mass spectrum of compound 5.
Fig. 4 is the hydrogen spectrum of probe BT-NH.
Fig. 5 is the carbon spectrum of probe BT-NH.
Fig. 6 is the mass spectrum of probe BT-NH.
Fig. 7 is the absorption and launching light spectrogram that probe BT-NH reacts front and back with NO.
Fig. 8 is probe BT-NH and NO response light spectrogram.
Fig. 9 is that probe BT-NH tests the jamming performance of common reactive oxygen species (ROS) reactive nitrogen species (RNS).
Figure 10 is that probe BT-NH tests 52 kinds of analyte jamming performances common in cell.
Figure 11 is detection of the probe BT-NH to HepG2 endogenous cellular NO.
Figure 12 is detection of the probe BT-NH to PD cell model NO.
Figure 13 is detection of the probe BT-NH to PD drosophila brain model NO.
Specific embodiment
Embodiment 1
A kind of preparation of the nitric oxide production near-infrared probe of quick response and the preparation method of biologic applications probe are as follows：
The synthesis of tributyl (the thio Fei Fen -2- base of 4- hexyl) stannane (1)
3- hexyl thiophene (2.50-10.00g) and the dry type tetrahydrofuran (50.00-200.00mL) of fresh distillation are placed in
In the mono- neck bottle of 250ml, in a nitrogen environment, after -78 DEG C are stirred 30 minutes, tributyltin chloride (8.16- is added dropwise
32.64mL in THF) stirring 2 hours.Then tributyl chlorination (5.08-20.30.00mL) is added.Mixture is placed in room
Temperature stirs 12 hours.After reaction, (50.00-200.00mL) is added in mixed liquor and is extracted with hexane.Organic layer nothing
Aqueous sodium persulfate is dry, and with solvent is removed in vacuo, obtains brown liquid compound 1.
The synthesis of benzo [c] [1,2,5] thiadiazoles (2)
O-phenylenediamine (2.50-10.00g) is added into 1000 milliliters of two-neck bottles, and is dissolved in methylene chloride
In the mixed solution of (100.00-400.00mL) and triethylamine (9.35-37.40g), Asia is then slowly added dropwise by dropping funel
Chlorosulfuric acid (1.85-7.40mL), until flowing back 20 hours after solid is completely dissolved.Mixture removes solvent under low pressure, then plus
Enter polyethylene (150.00-600.00mL) dissolution.By mixed liquor filtering and collecting filter liquid, solvent is removed in a vacuum, obtains palm fibre
Color solid chemical compound 2.
The synthesis of 4,7- dibromo benzo [c] [1,2,5] thiadiazoles (3)
Compound 2 (2.50-10.00g) is added in 500ml double-neck flask and is dissolved in hydrogen bromide (47%, 40.00-
In 160.00mL).Double necks will be slowly added to containing the hydrogen bromide (47%, 25.00-100.00mL) of bromine (8.80-35.20g)
In flask.After the entry to be completely, mixture is flowed back 6 hours, until forming orange solids precipitating.Object to be mixed is cooled to room temperature
Afterwards, it filters mixture and acquisition light yellow solid is washed with water.Solid is recrystallized with chloroform, obtains compound as white solid 3.
The synthesis of bromo- 5-6- dinitro benzo [c] [1,2, the 5]-thiadiazoles (4) of 4-7- bis-
At 0 DEG C, double necks containing trifluoromethanesulfonic acid (15.30-61.20g) are added dropwise in nitric acid (1.25-5.00g)
In flask, after stir about 30 minutes, compound 3 (2.50-10.00g) is added in mixed acid in 10 minutes.At 50 DEG C
After being stirred overnight, when only showing a spot with thin-layered chromatography (TLC) analysis mixed liquor, pour the mixture into ice water, mistake
It after filter obtains sediment, is washed with water, and with ethyl alcohol recrystallization purified product.Obtain yellow solid compound 4.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) -5,6- dinitro benzo [c] [1,2,5] thiadiazoles (5)
Compound 4 (1.00-4.00g) is first dissolved in tetrahydrofuran (10.00-40.00mL) and dimethyl carbonamidine
In the mixed liquor of (5.00-20.00mL), then in a nitrogen environment, by compound 1 (3.55-14.20g) and bi triphenyl phosphorus
Palladium chloride (0.02-0.10g) is added in solution.Mixture reacts overnight at 100 DEG C, and object to be mixed is cooled to room temperature
Afterwards, potassium fluoride (10.00-40.00mL) is added, after being filtered with Celite, collects filtrate and be concentrated.Product is through column chromatography (two
Chloromethanes:Polyethylene=1:10) it purifies, obtains orange solids compound 5.1H NMR(400MHz,CDCl3):δppm 7.32(s,
2H),7.31(s,2H),2.66(t,J1=7.6, J2=8.0Hz, 4H), 1.68-1.60 (m, 4H), 1.36-1.25 (m, 12H),
0.90(t,J1=6.4, J2=7.2Hz, 6H)13C NMR(100MHz,CDCl3):δppm 152.19,144.41,141.64,
132.17,129.21,126.43,121.40,31.65,30.32,30.26,28.90,22.62,14.11.MALDI-TOF-MS
(m/z):Calcd.for:C26H30N4O4S3([M+H]+):558.1429,found:559.0172.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) benzo [c] [1,2,5] thiadiazoles -5,6- diamines (BT-NH)
Under a nitrogen atmosphere, that compound 5 (0.50-2.00g) is dissolved in acetic acid (7.50-30.00mL) is inner, is then added
Iron (0.50-2.00g).It heats the mixture to 80 DEG C to react 6 hours, after object to be mixed is cooled to room temperature, be mentioned with ethyl acetate
Product is taken, and is washed with sodium hydrate aqueous solution.Solvent is removed under low pressure, chromatographs (ethyl acetate with column：Polyethylene=1：
10) purified product obtains yellow solid BT-NH.1H NMR(400MHz,CDCl3):δppm 7.18(s,2H),7.13(s,2H),
4.40(s,4H),2.70(dd,J1=7.6, J2=4.7Hz, 4H), 1.72-1.58 (m, 4H), 1.42-1.25 (m, 12H), 0.90
(t,J1=6.4, J2=6.4Hz, 6H)13C NMR(100MHz,CDCl3):δppm 150.90,143.66,139.23,
134.84,129.94,121.65,107.37,31.71,30.60,30.41,29.16,22.66,14.14.MALDI-TOF-MS
(m/z):Calcd.for:C26H34N4S3([M+H]+):498.1946,found:498.6180.
Embodiment 2
A kind of preparation of the nitric oxide production near-infrared probe of quick response and the preparation method of biologic applications probe are as follows：
The synthesis of tributyl (the thio Fei Fen -2- base of 4- hexyl) stannane (1)
The dry type tetrahydrofuran (50.00mL) of 3- hexyl thiophene (2.50g) and fresh distillation is placed in the mono- neck bottle of 250ml
In, in a nitrogen environment, after -78 DEG C are stirred 30 minutes, tributyltin chloride (8.16mL in THF) stirring 2 is added dropwise
Hour.Then tributyl chlorination (5.08mL) is added.Mixture is placed in room temperature, is stirred 12 hours.After reaction, it is mixing
Add (50.00mL) in liquid and is extracted with hexane.Organic layer is dry with anhydrous sodium sulfate, and with solvent is removed in vacuo, obtains brown
Liquid compound 1.
The synthesis of benzo [c] [1,2,5] thiadiazoles (2)
Into 1000 milliliters of two-neck bottles be added o-phenylenediamine (2.50g), and be dissolved in methylene chloride (100.00mL) and
In the mixed solution of triethylamine (9.35g), thionyl chloride (1.85mL) is then slowly added dropwise by dropping funel, until solid is complete
After fully dissolved, flow back 20 hours.Mixture removes solvent under low pressure, adds polyethylene (150.00mL) dissolution.It will mixing
Liquid filtering and collecting filter liquid, removes solvent in a vacuum, obtains brown solid compound 2.
The synthesis of 4,7- dibromo benzo [c] [1,2,5] thiadiazoles (3)
Compound 2 (2.50g) is added in 500ml double-neck flask and is dissolved in hydrogen bromide (47%, 40.00mL).It will
Hydrogen bromide (47%, 25.00mL) containing bromine (8.80g) is slowly added in double-neck flask.After the entry to be completely, by mixture
Reflux 6 hours, until forming orange solids precipitating.After object to be mixed is cooled to room temperature, filters mixture and acquisition is washed with water
Light yellow solid.Solid is recrystallized with chloroform, obtains compound as white solid 3.
The synthesis of bromo- 5-6- dinitro benzo [c] [1,2, the 5]-thiadiazoles (4) of 4-7- bis-
At 0 DEG C, nitric acid (1.25g) is added dropwise in the double-neck flask containing trifluoromethanesulfonic acid (15.30g), is stirred
After about 30 minutes, compound 3 (2.50g) is added in mixed acid in 10 minutes.After being stirred overnight at 50 DEG C, thin layer is used
It when chromatography (TLC) analysis mixed liquor only shows a spot, pours the mixture into ice water, after sediment is obtained by filtration, uses
Water washing, and with ethyl alcohol recrystallization purified product.Obtain yellow solid compound 4.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) -5,6- dinitro benzo [c] [1,2,5] thiadiazoles (5)
Compound 4 (1.00g) is first dissolved in the mixed liquor of tetrahydrofuran (10.00mL) and dimethyl carbonamidine (5.00mL)
In, then in a nitrogen environment, compound 1 (3.55g) and bi triphenyl phosphorus palladium chloride (0.02g) are added in solution.
Mixture reacts overnight at 100 DEG C, after object to be mixed is cooled to room temperature, is added potassium fluoride (10.00mL), is filtered with Celite
Afterwards, it collects filtrate and is concentrated.Product is through column chromatography (methylene chloride:Polyethylene=1:10) it purifies, obtains orange solids chemical combination
Object 5.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) benzo [c] [1,2,5] thiadiazoles -5,6- diamines (BT-NH)
Under a nitrogen atmosphere, that compound 5 (0.50g) is dissolved in acetic acid (7.50mL) is inner, and iron (0.50g) then is added.
It heats the mixture to 80 DEG C to react 6 hours, after object to be mixed is cooled to room temperature, is extracted with ethyl acetate product, and use hydrogen-oxygen
Change sodium water solution washing.Solvent is removed under low pressure, chromatographs (ethyl acetate with column：Polyethylene=1：10) purified product obtains
Yellow solid BT-NH.
Embodiment 3
A kind of preparation of the nitric oxide production near-infrared probe of quick response and the preparation method of biologic applications probe are as follows：
The synthesis of tributyl (the thio Fei Fen -2- base of 4- hexyl) stannane (1)
The dry type tetrahydrofuran (200.00mL) of 3- hexyl thiophene (10.00g) and fresh distillation is placed in the mono- neck bottle of 250ml
In, in a nitrogen environment, after -78 DEG C are stirred 30 minutes, tributyltin chloride (32.64mL in THF) stirring 2 is added dropwise
Hour.Then tributyl chlorination (20.30.00mL) is added.Mixture is placed in room temperature, is stirred 12 hours.After reaction, exist
Add (200.00mL) in mixed liquor and is extracted with hexane.Organic layer is dry with anhydrous sodium sulfate, and with solvent is removed in vacuo, obtains
Brown liquid compound 1.
The synthesis of benzo [c] [1,2,5] thiadiazoles (2)
Into 1000 milliliters of two-neck bottles be added o-phenylenediamine (10.00g), and be dissolved in methylene chloride (400.00mL) and
In the mixed solution of triethylamine (37.40g), thionyl chloride (7.40mL) is then slowly added dropwise by dropping funel, until solid
After being completely dissolved, flow back 20 hours.Mixture removes solvent under low pressure, adds polyethylene (600.00mL) dissolution.It will mix
Liquid filtering and collecting filter liquid is closed, solvent is removed in a vacuum, obtains brown solid compound 2.
The synthesis of 4,7- dibromo benzo [c] [1,2,5] thiadiazoles (3)
Compound 2 (10.00g) is added in 500ml double-neck flask and is dissolved in hydrogen bromide (47%, 160.00mL).
It will be slowly added in double-neck flask containing the hydrogen bromide (47%, 100.00mL) of bromine (35.20g).After the entry to be completely, it will mix
It closes object to flow back 6 hours, until forming orange solids precipitating.After object to be mixed is cooled to room temperature, filters mixture and be washed with water
Obtain light yellow solid.Solid is recrystallized with chloroform, obtains compound as white solid 3.
The synthesis of bromo- 5-6- dinitro benzo [c] [1,2, the 5]-thiadiazoles (4) of 4-7- bis-
At 0 DEG C, nitric acid (5.00g) is added dropwise in the double-neck flask containing trifluoromethanesulfonic acid (61.20g), is stirred
After about 30 minutes, compound 3 (10.00g) is added in mixed acid in 10 minutes.After being stirred overnight at 50 DEG C, use is thin
When layer chromatography (TLC) analysis mixed liquor only shows a spot, pour the mixture into ice water, after sediment is obtained by filtration,
It is washed with water, and with ethyl alcohol recrystallization purified product.Obtain yellow solid compound 4.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) -5,6- dinitro benzo [c] [1,2,5] thiadiazoles (5)
Compound 4 (4.00g) is first dissolved in the mixing of tetrahydrofuran (40.00mL) and dimethyl carbonamidine (20.00mL)
In liquid, then in a nitrogen environment, compound 1 (14.20g) and bi triphenyl phosphorus palladium chloride (0.10g) are added to solution
In.Mixture reacts overnight at 100 DEG C, after object to be mixed is cooled to room temperature, is added potassium fluoride (40.00mL), uses Celite
After filtering, collects filtrate and be concentrated.Product is through column chromatography (methylene chloride:Polyethylene=1:10) it purifies, obtains orange solids
Compound 5.
The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) benzo [c] [1,2,5] thiadiazoles -5,6- diamines (BT-NH)
Under a nitrogen atmosphere, that compound 5 (2.00g) is dissolved in acetic acid (30.00mL) is inner, and iron (2.00g) then is added.
It heats the mixture to 80 DEG C to react 6 hours, after object to be mixed is cooled to room temperature, is extracted with ethyl acetate product, and use hydrogen-oxygen
Change sodium water solution washing.Solvent is removed under low pressure, chromatographs (ethyl acetate with column：Polyethylene=1：10) purified product obtains
Yellow solid BT-NH.
Embodiment 4
A kind of preparation and biologic applications of the nitric oxide production near-infrared probe of quick response, can detecte organism and
The content of NO in PD cell and transgenic drosophila model：
Fig. 7 probe BT-NH reacts the absorption and launching light spectrogram of front and back with NO.In PBS：HAc(v:V)=1:In 1 solution,
Detect the absorption and transmitting fluorescence spectra of the NO of 20 μM of BT-NH and 20 μM of BT-NH and 5 times of equivalents.Excitation wavelength is
525nm, receiving wavelength is 560-800nm.
Fig. 8 probe BT-NH and NO response light spectrogram.In PBS：HAc(v:V)=1:In 1 solution, detect 20 μM of BT-NH with
Fluorescence spectra after various concentration NO reaction 30 minutes.Excitation wavelength is 525nm, and receiving wavelength is 560-800nm.
Fig. 9 probe BT-NH tests the jamming performance of common reactive oxygen species (ROS) reactive nitrogen species (RNS).?
PBS：HAc(v:V)=1:In 1 solution, the NO and .O of 20 μM of BT-NH and 5 times of equivalents are detected2, ROO-, H2O2,-OH-, O2-,
ONOO-, ClO-Fluorescence spectra after reaction 30 minutes.Excitation wavelength is 525nm, and receiving wavelength is 560-800nm.
Figure 10 probe BT-NH tests 52 kinds of analyte jamming performances common in cell.In PBS：HAc(v:V)=1:1
In solution, existing metal ion in the NO and organism of 20 μM of BT-NH and 5 times of equivalents is detected, anion and amino acid are anti-
Fluorescence spectra after answering 30 minutes.This 52 kinds of analytes are K respectively+、Ca2+、Mn2+、Cr2+、Co2+、Ni2+、Fe2+、Fe3+、
Ba2+、Mg2+、Al3+、Ag+、Cd2+、Na+、Zn2+、Cu2+、I-、Cl-、Br-、F-、SO4 2-、HPO4 2-、HCO3 -、NO3、S2-、CO3 2-、
Ac-、HS-、H2PO4-、SO3 2-SCN-、PO4 3-, tyrosine, isoleucine, valine, alanine, aspartic acid, histidine, half Guang
Propylhomoserin, ornithine, proline, glutamic acid, glycine, tryptophan, arginine, serine, threonine, phenylalanine, first sulphur ammonia
Acid, cystine, 2,6- diaminocaproic acid.Excitation wavelength is 525nm, and receiving wavelength is that 560-800nm (takes fluorescence at 620nm strong
Degree).
Detection of Figure 11 probe BT-NH to HepG2 endogenous cellular NO.By HepG2 cell inoculation in the glass bottom of 30mm
In culture dish, when cell confluency degree reaches 60-70%, the culture medium of HepG2 cell is changed to containing LPS (20mg mL-1) and
IFN-γ(0.05μg mL-1) culture medium be incubated for 12 hours be used as stimulation group.Meanwhile accordingly by other disk HepG2 cell
Culture medium be changed to containing LPS (20mg mL-1), IFN-γ (0.05 μ g mL-1) and L-NAME (2mM) culture medium be incubated for 12
Hour is used as inhibition group.It sets up one and the cell of drug is not added as a control group.After 12 hours, culture medium is sucked out, addition contains
The culture medium of 20 μM of BT-NH continues to be incubated for 4 hours.Then culture medium is removed, after washing 3 times with PBS, 1mL PBS is added, is used for
Cell imaging.Excitation wavelength is 545nm, and receiving wavelength is 560-700nm.
Detection of Figure 12 probe BT-NH to PD cell model NO.By SH-SY5Y cell inoculation in the glass bottom culture of 30mm
In ware, when cell confluency degree reaches 60-70%, culture medium is changed to containing LPS (20mg mL-1) culture medium be incubated for it is 12 small
Shi Zuowei stimulation group.It sets up one and the cell of LPS is not added as a control group.After 12 hours, culture medium is sucked out, is added and contains 20 μM
The culture medium of BT-NH continues to be incubated for 4 hours.Then remove culture medium, after washing 3 times with PBS, be added 1mL PBS, for cell at
Picture.Excitation wavelength is 545nm, and receiving wavelength is 560-700nm.
Detection of Figure 13 probe BT-NH to PD drosophila brain model NO.Screen the Pakin null fruit that 10 ages are 20 days
Fly screens the Yellow-white drosophila of 10 same ages as a control group as experimental group.Screen other 10 phase the same years
The Yellow-white drosophila in age is as blank control group.After dissecting drosophila brain, by 10 Pakin null drosophilas and 10
Yellow-white drosophila is placed in the PBS containing 50 μM of BT-NH and is incubated for 6 hours, by other 10Yellow-white drosophila
It is placed in PBS and is incubated for 6 hours.It after incubation, after the PBS rinse three times of drosophila brain, is placed on glass slide, is used for drosophila
Brian Imaging.Excitation wavelength is 545nm, and receiving wavelength is 560-700nm.
Claims (8)
1. a kind of nitric oxide production near-infrared probe of quick response, it is characterised in that：The fluorescence probe is BT-NH fluorescence
Probe, structure is as shown in I：
2. the nitric oxide production near-infrared probe of quick response according to claim 1, it is characterised in that：Introduce adjacent benzene two
Amine introduces the solubility that hexyl alkyl chain improves probe as NO acquirer.
3. the preparation method of the nitric oxide production near-infrared probe of quick response according to claim 1, it is characterised in that：
The probe to prepare route schema as follows：
Step 1：The synthesis of tributyl (the thio Fei Fen -2- base of 4- hexyl) stannane (1)
It is mono- that the dry type tetrahydrofuran 50.00-200.00mL of 3- hexyl thiophene 2.50-10.00g and fresh distillation are placed in 250ml
In neck bottle, in a nitrogen environment, after -78 DEG C are stirred 30 minutes, tributyltin chloride 8.16-32.64mL in is added dropwise
THF is stirred 2 hours, and tributyl chlorination 5.08-20.30.00mL is then added, and mixture is placed in room temperature, stirs 12 hours, instead
After answering, 50.00-200.00mL is added in mixed liquor and is extracted with hexane, organic layer is dry with anhydrous sodium sulfate, and with very
Sky removal solvent, obtains brown liquid compound 1；
Step 2：The synthesis of benzo [c] [1,2,5] thiadiazoles (2)
O-phenylenediamine 2.50-10.00g is added into 1000 milliliters of two-neck bottles, and is dissolved in methylene chloride 100.00-
In the mixed solution of 400.00mL and triethylamine 9.35-37.40g, thionyl chloride 1.85- is then slowly added dropwise by dropping funel
7.40mL, until flowing back 20 hours, mixture removes solvent under low pressure, adds polyethylene after solid is completely dissolved
150.00-600.00mL dissolution, by mixed liquor filtering and collecting filter liquid, removes solvent in a vacuum, obtains brown solid chemical combination
Object 2；
Step 3：The synthesis of 4,7- dibromo benzo [c] [1,2,5] thiadiazoles (3)
2 2.50-10.00g of compound is added in 500ml double-neck flask and is dissolved in hydrogen bromide 47%, 40.00-160.00mL
In, by the hydrogen bromide 47% containing bromine 8.80-35.20g, 25.00-100.00mL is slowly added in double-neck flask, to complete
After addition, mixture is flowed back 6 hours, until forming orange solids precipitating.After object to be mixed is cooled to room temperature, mixture is filtered
And acquisition light yellow solid is washed with water, solid is recrystallized with chloroform, obtains compound as white solid 3；
Step 4：The synthesis of bromo- 5-6- dinitro benzo [c] [1,2, the 5]-thiadiazoles (4) of 4-7- bis-
At 0 DEG C, nitric acid 1.25-5.00g is added dropwise in the double-neck flask containing trifluoromethanesulfonic acid 15.30-61.20g, is stirred
After mixing about 30 minutes, 3 2.50-10.00g of compound is added in mixed acid in 10 minutes, is stirred overnight at 50 DEG C
Afterwards, it when only showing a spot with thin-layered chromatography TLC analysis mixed liquor, pours the mixture into ice water, precipitating is obtained by filtration
It after object, is washed with water, and with ethyl alcohol recrystallization purified product.Obtain yellow solid compound 4；
Step 5：The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) -5,6- dinitro benzo [c] [1,2,5] thiadiazoles (5)
4 1.00-4.00g of compound is first dissolved in tetrahydrofuran 10.00-40.00mL and dimethyl carbonamidine 5.00-20.00mL
Mixed liquor in, then in a nitrogen environment, by 1 3.55-14.20g of compound and bi triphenyl phosphorus palladium chloride 0.02-
0.10g is added in solution, and mixture reacts overnight at 100 DEG C, and after object to be mixed is cooled to room temperature, potassium fluoride is added
10.00-40.00mL after being filtered with Celite, collects filtrate and is concentrated, product is through column chromatography methylene chloride:Polyethylene=1:
10 purifying, obtain orange solids compound 5；
Step 6：The synthesis of 4,7- bis- (4- hexyl thiophene -2- base) benzo [c] [1,2,5] thiadiazoles -5,6- diamines (BT-NH)
Under a nitrogen atmosphere, 5 0.50-2.00g of compound is dissolved in acetic acid 7.50-30.00mL, iron 0.50- is then added
2.00g heats the mixture to 80 DEG C and reacts 6 hours, after object to be mixed is cooled to room temperature, is extracted with ethyl acetate product, and
It is washed with sodium hydrate aqueous solution, removes solvent under low pressure, chromatograph ethyl acetate with column：Polyethylene=1：10 purified products,
Obtain yellow solid BT-NH.
4. the preparation method of the nitric oxide production near-infrared probe of quick response according to claim 3, it is characterised in that：
The molar ratio of 3- hexyl thiophene and lithium diisopropylamine is 1 in the step (1)：1.0-1：1.2；3- hexyl thiophene and three fourths
The molar ratio of base stannic chloride is 1：1.0-1：1.1；The molar ratio of o-phenylenediamine and thionyl chloride is 1 in the step (2)：1.0-
1：1.3；Step (3) compound 2 and the molar ratio of bromine are 1：2.0-1：4.0；Step (4) compound 3 and smoke
The molar ratio of nitric acid is 1：2.0-1：4.0；Fuming nitric aicd and trifluoromethanesulfonic acid molar ratio are 1：3.0-1：4.0；Step (5) is described
The molar ratio of compound 4 and chemical combination 1 is 1：2.0-1：2.5；The molar ratio of compound 4 and bi triphenyl phosphorus palladium chloride is 1：
0.03-1：0.1；Step (6) is described, and the molar ratio of compound 5 and iron powder is 1：7.0-1：12.0.
5. the preparation method of the nitric oxide production near-infrared probe of quick response according to claim 3, it is characterised in that：
The molar ratio of 3- hexyl thiophene and lithium diisopropylamine is 1 in the step (1)：1.0-1：1.1；3- hexyl thiophene and three fourths
The molar ratio of base stannic chloride is 1：1.0-1：1.05；The molar ratio of o-phenylenediamine and thionyl chloride is 1 in the step (2)：
1.0-1：1.1；Step (3) compound 2 and the molar ratio of bromine are 1：2.5-1：3.0；Step (4) compound 3
Molar ratio with fuming nitric aicd is 1：3.0-1：4.0；Fuming nitric aicd and trifluoromethanesulfonic acid molar ratio are 1：3.0-1：3.5；Step
(5) molar ratio of the compound 4 and chemical combination 1 is 1：2.1-1：2.2；Mole of compound 4 and bi triphenyl phosphorus palladium chloride
Than being 1：0.03-1：0.05；Step (6) is described, and the molar ratio of compound 5 and iron powder is 1：7.0-1：10.0.
6. a kind of biologic applications of the nitric oxide production near-infrared probe of quick response according to claim 1, described
Fluorescence probe can be applied to the NO for accurately detecting endogenous cellular.
7. a kind of biologic applications of the nitric oxide production near-infrared probe of quick response according to claim 1, described
Fluorescence probe can be applied to the endogenous NO for accurately detecting PD cell model.
8. a kind of biologic applications of the nitric oxide production near-infrared probe of quick response according to claim 1, described
Fluorescence probe can be applied to the endogenous NO for accurately detecting PD drosophila brain model.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810600223.XA CN108864071A (en) | 2018-06-12 | 2018-06-12 | A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810600223.XA CN108864071A (en) | 2018-06-12 | 2018-06-12 | A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108864071A true CN108864071A (en) | 2018-11-23 |
Family
ID=64338083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810600223.XA Pending CN108864071A (en) | 2018-06-12 | 2018-06-12 | A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108864071A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113462381A (en) * | 2020-03-30 | 2021-10-01 | 首都师范大学 | Polar sensitive NIR probe with high binding force with amyloid fiber and preparation and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101270342A (en) * | 2008-03-28 | 2008-09-24 | 南京大学 | Tumour targeting fluorescent probe and application in tumour NO test |
| CN102617467A (en) * | 2012-02-21 | 2012-08-01 | 大连理工大学 | Ultrahigh-sensitivity fluorescent probe for detecting nitrogen monoxide |
| CN106432178A (en) * | 2016-08-31 | 2017-02-22 | 南京工业大学 | Nitric oxide probe based on fluorescent double-response mechanism and synthesis and application thereof |
| CN108129495A (en) * | 2018-01-17 | 2018-06-08 | 南京工业大学 | A kind of organic semiconductor of near-infrared containing selenium and its preparation method and application |
-
2018
- 2018-06-12 CN CN201810600223.XA patent/CN108864071A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101270342A (en) * | 2008-03-28 | 2008-09-24 | 南京大学 | Tumour targeting fluorescent probe and application in tumour NO test |
| CN102617467A (en) * | 2012-02-21 | 2012-08-01 | 大连理工大学 | Ultrahigh-sensitivity fluorescent probe for detecting nitrogen monoxide |
| CN106432178A (en) * | 2016-08-31 | 2017-02-22 | 南京工业大学 | Nitric oxide probe based on fluorescent double-response mechanism and synthesis and application thereof |
| CN108129495A (en) * | 2018-01-17 | 2018-06-08 | 南京工业大学 | A kind of organic semiconductor of near-infrared containing selenium and its preparation method and application |
Non-Patent Citations (3)
| Title |
|---|
| ELIF KOSE UNVER ET AL.: "Synthesis of new donor–acceptor polymers containing thiadiazoloquinoxaline and pyrazinoquinoxaline moieties:low-band gap, high optical contrast, and almost black colored materials", 《TETRAHEDRON LETTERS》 * |
| QIAN JIANG ET AL.: "A novel nitro-substituted benzothiadiazole as fluorescent probe for tumor cells under hypoxic condition", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| YOONKYOO LEE ET AL.: "Synthesis and photovoltaic properties of low-bandgap alternating copolymers consisting of 3-hexylthiophene and [1,2,5]thiadiazolo[3,4-g]quinoxaline derivatives", 《ORGANIC ELECTRONICS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113462381A (en) * | 2020-03-30 | 2021-10-01 | 首都师范大学 | Polar sensitive NIR probe with high binding force with amyloid fiber and preparation and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xie et al. | A turn-off fluorescent probe for the detection of Cu 2+ based on a tetraphenylethylene-functionalized salicylaldehyde Schiff-base | |
| Liao et al. | A novel acylhydrazone-based derivative as dual-mode chemosensor for Al3+, Zn2+ and Fe3+ and its applications in cell imaging | |
| Dong et al. | A novel ferrocenyl-based multichannel probe for colorimetric detection of Cu (II) and reversible fluorescent “turn-on” recognition of Hg (II) in aqueous environment and living cells | |
| Fan et al. | 4-(8′-Hydroxyquinolin-7′-yl) methyleneimino-1-phenyl-2, 3-dimethyl-5-pyzole as a fluorescent chemosensor for aluminum ion in acid aqueous medium | |
| CN110283583B (en) | Gamma-glutamyl transpeptidase responsive molecular probe and application thereof | |
| CN105712964B (en) | Preparation method and application of thiol fluorescent probe based on coumaroyl hydrazide | |
| CN104004514B (en) | A kind of detect trivalent bismuth ion symmetric double Rhodamine fluorescent probe and preparation method and purposes | |
| CN102746313A (en) | Rhodamine-B hydrazide derivative containing 1,2,4-triazole structural unit, preparation method and application thereof | |
| CN104804728A (en) | Preparation and application of fluorescence-enhanced thiophenol fluorescence probe | |
| CN107311957A (en) | One kind is based on aggregation-induced emission and excited state intramolecular proton transfer compound and its preparation method and application | |
| CN107602417A (en) | It is a kind of based on aggregation-induced emission mechanism can quick detection zinc ion fluorescence probe and preparation method and application | |
| CN104845612A (en) | Polystyrene mercury ion fluorescence recognition materials and preparation method thereof | |
| CN111808109B (en) | Pyridazine quinoxaline diamine Schiff base cobalt ion fluorescent probe and preparation method thereof | |
| CN104277061A (en) | Boric acid fluorescence molecular probe as well as preparation method and application thereof | |
| Yan et al. | A new dual-function fluorescent probe of Fe3+ for bioimaging and probe-Fe3+ complex for selective detection of CN− | |
| Cui et al. | A rhodamine B-based turn on fluorescent probe for selective recognition of mercury (II) ions | |
| CN105542755B (en) | A kind of fluorescence probe based on polypeptide recognition group, its preparation method and its detection method to copper ion and cyanide ion | |
| CN105884713A (en) | Fluorescence-enhanced hydrogen sulfide molecular fluorescent probe and preparation method and application thereof | |
| CN108864071A (en) | A kind of nitric oxide production near-infrared probe of quick response and its preparation and biologic applications | |
| CN109206351A (en) | A kind of near infrared fluorescent probe, preparation method and application for surveying palladium ion based on flower cyanines structure | |
| CN108752275A (en) | A kind of pH fluorescence probes and its preparation method and application | |
| CN110357896B (en) | Compound, preparation and application thereof in detecting divalent copper ions and strong acid pH | |
| CN108864159A (en) | A kind of pyrroles can be used for detecting Fe3+ under acidic environment-benzene boron fluorine fluorescent chemicals and preparation method thereof | |
| CN107235985A (en) | A kind of fluorescence probe for detecting bivalent cupric ion and preparation method and application | |
| CN106928133A (en) | A kind of switching mode bivalent cupric ion fluorescence probe and its preparation and application |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181123 |
|
| WD01 | Invention patent application deemed withdrawn after publication |