CN105017297A - 一种氟硼吡咯类衍生荧光化合物及其应用 - Google Patents
一种氟硼吡咯类衍生荧光化合物及其应用 Download PDFInfo
- Publication number
- CN105017297A CN105017297A CN201410173946.8A CN201410173946A CN105017297A CN 105017297 A CN105017297 A CN 105017297A CN 201410173946 A CN201410173946 A CN 201410173946A CN 105017297 A CN105017297 A CN 105017297A
- Authority
- CN
- China
- Prior art keywords
- phthalic acid
- compound
- fluorescent
- formula
- fluoboric
- 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
- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 26
- 150000003233 pyrroles Chemical class 0.000 title abstract 5
- 238000001514 detection method Methods 0.000 claims abstract description 16
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 21
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 20
- JGUQGWIAGYEIDB-UHFFFAOYSA-N C(C=1C(C(=O)O)=CC=CC1)(=O)O.[S] Chemical compound C(C=1C(C(=O)O)=CC=CC1)(=O)O.[S] JGUQGWIAGYEIDB-UHFFFAOYSA-N 0.000 claims description 16
- BYKWWKHOEHNPJG-UHFFFAOYSA-N C(C=1C(C(=O)O)=CC=CC1)(=O)O.[Se] Chemical compound C(C=1C(C(=O)O)=CC=CC1)(=O)O.[Se] BYKWWKHOEHNPJG-UHFFFAOYSA-N 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 229910052714 tellurium Inorganic materials 0.000 claims description 10
- LIQLLTGUOSHGKY-UHFFFAOYSA-N [B].[F] Chemical compound [B].[F] LIQLLTGUOSHGKY-UHFFFAOYSA-N 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 210000004027 cell Anatomy 0.000 claims description 7
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims description 6
- NMILGIZTAZXMTM-UHFFFAOYSA-N 4-propylmorpholine Chemical group CCCN1CCOCC1 NMILGIZTAZXMTM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- FXURYRWDOBBQLX-UHFFFAOYSA-N N1C=CC=C1.[B].[F] Chemical class N1C=CC=C1.[B].[F] FXURYRWDOBBQLX-UHFFFAOYSA-N 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 claims description 2
- 210000003712 lysosome Anatomy 0.000 claims description 2
- 230000001868 lysosomic effect Effects 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 34
- -1 pyrrole derivative compound Chemical class 0.000 abstract description 7
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 206010027476 Metastases Diseases 0.000 abstract 1
- 230000006907 apoptotic process Effects 0.000 abstract 1
- 210000004204 blood vessel Anatomy 0.000 abstract 1
- 230000009401 metastasis Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 102100035429 Cystathionine gamma-lyase Human genes 0.000 description 4
- 108010045283 Cystathionine gamma-lyase Proteins 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000002189 fluorescence spectrum Methods 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010025 steaming Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 2
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960002663 thioctic acid Drugs 0.000 description 2
- 229960004441 tyrosine Drugs 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 229940116269 uric acid Drugs 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- CWHJIJJSDGEHNS-MYLFLSLOSA-N Senegenin Chemical compound C1[C@H](O)[C@H](O)[C@@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)C(CC[C@]4(CCC(C[C@H]44)(C)C)C(O)=O)=C4[C@@H](CCl)C[C@@H]3[C@]21C CWHJIJJSDGEHNS-MYLFLSLOSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000804 electron spin resonance spectroscopy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 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 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000003975 mesenteric artery Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000009871 tenuigenin Substances 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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
- 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
-
- 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
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1022—Heterocyclic compounds bridged by heteroatoms, e.g. N, P, Si or B
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
本发明涉及用于检测硫化氢(H2S)的荧光探针，具体的说是一种氟硼吡咯类衍生荧光化合物及其应用。氟硼吡咯类衍生荧光化合物如通式Ⅰ所示，并以所述氟硼吡咯类化合物作为H2S的荧光探针。本发明H2S荧光探针的这类化合物，在H2S存在下对应的荧光强度发生变化，可用于H2S的检测，并可大大降低外部检测条件的干扰，提高检测精度。这类化合物作为荧光探针可用于细胞内外H2S的检测，不仅对阐明H2S对血管新生产生具有重要的科学意义，而且为H2S在不同浓度下对肿瘤凋亡和转移奠定理论基础。
Description
技术领域
本发明涉及用于检测硫化氢(H2S)的荧光探针，具体的说是一种氟硼吡咯类衍生荧光化合物及其应用。
背景技术
目前认为硫化氢(H2S)是继NO和CO之后被发现的第三种气体信号分子，内源性H2S在体内由不同的组织和细胞产生，在生理浓度水平下，H2S参与一系列的生理调控过程，与此同时，三个气体递质硫化氢、一氧化氮和一氧化碳之间还通过各种交互作用调控着人体的健康与疾病，但目前对H2S的了解远少于NO和CO。内源性H2S作为小分子物质，在脂溶性溶剂中的溶解度为水中的5倍，可自由通过细胞膜。H2S在线粒体内谷胱甘肽作用下被氧化为硫酸盐和硫代硫酸盐，在细胞质中少量H2S通过甲基化作用转变为低毒的甲硫醇和二甲基硫酸盐，通过肾脏、肠道和肺脏排出。
哺乳动物体内的H2S主要通过含硫的半胱氨酸代谢生成。胱硫醚-γ-裂解酶(eystathionine-γ-lyase，CSE)和胱硫醚-β-合成酶(cystathionine-β-synthase，CBS)是体内转硫途径的关键酶，对H2S的产生以及含硫化合物的代谢具有重要调节作用，CSE主要在主动脉、肺动脉、尾动脉、肠系膜动脉和门静脉上有表达；相反CBS主要分布在神经系统内；在回肠、肾脏和肝脏中则同时有CBS和CSE的表达；一些种类的癌细胞也可产生H2S。
传统的气体检测方法有电化学法、化学发光法、电子自旋共振波谱法和紫外可见光谱法等，但上述方法往往需要试样预处理，需要破坏组织或裂解细胞，并且耗时长，相对成本较高。故而，上述检测方法不能直接检测细胞内硫化氢的真实状态和浓度，难以真正反映细胞内硫化氢原位实时活动规律及调控机制。因此，实验技术已经大大地影响到对硫化氢的检测以及其效应信号通道的研究。虽然上述每一种方法在一定条件下都是可行的，但是关于生命体中H2S的研究所遇到的瓶颈是缺少灵敏而又专一地检测生命系统中H2S靶向浓度变化的检测工具，由此可见，开发一种新的能够实现对生命体内H2S水平进行靶向检测的生物医学工具将是该研究领域的突破点。
发明内容
本发明的目的在于提供一种氟硼吡咯类衍生荧光化合物及其应用。
为实现上述目的，本发明采用的技术方案为：
一种氟硼吡咯类衍生荧光化合物，如通式Ⅰ所示，
通式Ⅰ中：
R1为连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团；
R2为连硫邻苯二甲酸、连硒邻苯二甲酸、连碲邻苯二甲酸基团、丁基三苯基基团、N-丙基吗啉基团或C1-25的烷基链；
X为H或卤素；
Y为N或C；
Z为N或O；
进一步的说，所述通式Ⅰ中R1为连硫邻苯二甲酸；R2为丁基三苯基基团或N-丙基吗啉基团；X为H；Y为N；Z为O。
一种氟硼吡咯类化合物的应用，以所述通式Ⅰ所示的氟硼吡咯类化合物作为硫化氢的荧光探针。
一种荧光探针，荧光探针为通式Ⅰ所示的以(BODIPY)染料作为荧光母体，并在母体上R2取代基位置引入对具备线粒体、溶酶体、内质网定位功能团的季磷盐、吗啉、C1-25烷基碳链、连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团。
所述荧光探针用于定性/定量的检测生理环境下、细胞或生物体内的硫化氢。
本发明的有益效果：
本发明化合物用于作为H2S荧光检测的探针，其在H2S存在下对应的荧光强度发生变化，进而可用于水体系、模拟生理环境和细胞内HNO水平的检测。本发明用于H2S荧光探针的这类化合物，在H2S存在下对应的荧光强度发生变化，可用于H2S的检测，并可缩减样品处理时间、大大降低检测成本和提高检测精度。这类化合物作为荧光探针可用于细胞内外H2S浓度的检测，不仅对阐明H2S对血管新生产生具有重要的科学意义，而且为H2S在不同浓度下对肿瘤凋亡和转移奠定理论基础。
附图说明
图1为本发明实施例提供的采用的荧光探针对H2S检测前后荧光变化。
图2为本发明实施例提供的所采用的荧光探针对H2S的选择性示意图；其中，横坐标从左至右依次为：硫化氢、谷胱甘肽、半胱氨酸、硫代硫酸钠、亚硫酸氢钠、维生素C、硫辛酸、环氧硫蛋白、金属硫蛋白、维生素E、尿酸、组氨酸和酪氨酸。
具体实施方式
氟硼吡咯类衍生荧光化合物通式为：
式Ⅰ中：
R1为连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团；
R2为连硫邻苯二甲酸、连硒邻苯二甲酸、连碲邻苯二甲酸基团、丁基三苯基基团、N-丙基吗啉基团或C1-25的烷基链；
X为H或卤素；
Y为N或C；
Z为N或O；
优选：通式Ⅰ中X为H；Y为N；Z为O时，所述氟硼吡咯类化合物的通式为：
通式II中：
R1为连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团；
R2为连硫邻苯二甲酸、连硒邻苯二甲酸、连碲邻苯二甲酸基团、丁基三苯基基团或N-丙基吗啉基团；
将通式Ⅰ与待测定水体、模拟生理环境或细胞内的H2S反应从而导致荧光强度的改变，所得通式III结构的化合物；
将通式II结构应用于检测H2S时，其与H2S作用后，生成具有通式IV结构的化合物，从而导致荧光强度的改变；
通式II可对H2S进行定性、定量的检测。
本发明中使用的术语“烷基”包括直链烷基和支链烷基。如提及单个烷基如“丙基”，则只特指直链烷基，如提及单个支链烷基如“异丙基”，则只特指支链烷基。例如，“C1-6烷基”包括C1-4烷基、C1-3烷基、甲基、乙基、正丙基、异丙基和叔丁基。类似的规则也适用于本说明书中使用的其它基团。
本发明中使用的术语“卤素”包括氟、氯、溴和碘。
本发明中使用的术语“苄基”是指-CH2-Ph基团。当用“任选取代”修饰苄基时，指该苄基可以未取代的形式存在，或者可被合适的取代基在任何合适的位置取代。合适的取代基包括但不限于H、C1-18烷基、CN、COOH、NH2、NO2、OH、SH、C1-6烷氧基、C1-6烷基氨基、C1-6酰氨基、卤素、或C1-6卤代烷基等，只要最终形成的化合物具有本发明期望的性质。优选苄基由COOH、NH2、OH、C1-6烷氧基、卤素任选取代。
具体实施方式
实施例用于进一步说明本发明，但本发明不限于实施例。
实施例1.氟硼吡咯类衍生荧光化合物的制备：
通式Ⅰ中所示氟硼吡咯类化合物由市售对羟基苯乙酮和苯甲醛反应起，合成响应的荧光团BODIPY，然后在荧光团相应的位置分别修饰上不同的定位基团。最后将修饰定位基团的荧光团与连硫邻苯二甲酸在二氯甲烷溶剂中，由DMAP和EDC催化反应生成相应的氟硼吡咯类衍生荧光化合物。具体实施例如下：
制备式一化合物：
在氩气保护下，BODIPY荧光团(52.9mg，0.1mmol)及连硫邻苯二甲酸(67.4mg，0.22mmol)、DMAP(24.4mg，0.2mmol)、EDCI(19.2mg，0.1mmol)溶于盛有20ml干燥的二氯甲烷的50ml烧瓶中，常温条件下搅拌24h，TLC追踪反应进度。粗产品由氢溴酸中和后由NaBr的饱和溶液洗涤至中性，二氯甲烷萃取，硫酸钠干燥有机层后旋蒸。采用柱层析(200-300目)分离法对产品进行分离，洗脱剂为甲醇。收集绿色组分，蒸干溶剂后得到式一所示化合物33mg,收率:30％。
化合物式一的1H NMR(500MHz,CDCl3-D1)δ(ppm):6.76(s,2H),7.20-7.90(m,32H),8.35(d,2H),12.75(s,2H).LC-MS(API-ES):m/zC60H38BF2N3O8S4Calcd1105.1603,found[M-H]-1104.1529.
制备式二化合物：
在氩气保护下，取连有三苯基膦基团的荧光团(84.6mg，0.1mmol)及连硫邻苯二甲酸(33.7mg，0.11mmol)、DMAP(12.2mg，0.1mmol)、EDCI(9.6mg，0.05mmol)于盛有20ml干燥的二氯甲烷的50ml烧瓶中，常温下搅拌24h，TLC追踪反应进度。粗产品由氢溴酸中和后，用NaBr的饱和溶液洗涤至中性，二氯甲烷萃取，硫酸钠干燥有机层后旋蒸。所得固体用二氯甲烷溶解后，用硅胶柱色谱(200-300目)分离。洗脱剂为乙酸乙酯和甲醇梯度洗脱(2:1-0:1/v/v)，收集绿色组分，蒸干溶剂后得到式二所示化合物27.2mg,收率:24％。
式二化合物的1H NMR(500MHz,CDCl3-D1)δ(ppm):1.32-1.57(m,6H),4.07(t,2H),6.60(s,2H),6.99-7.85(m,39H),8.41(s,2H),12.73(s,1H).LC-MS(API-ES):m/z C68H52BF2N3O5PS2 +Calcd1134.3142,found[M+]1134.3141.
制备式三化合物：
取已制备的连有线粒体定位基团的荧光团(84.6mg，0.1mmol)及连硫邻苯二甲酸(33.7mg，0.11mmol)、4-二甲氨基吡啶DMAP(12.2mg，0.1mmol)、1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐EDCI(9.6mg，0.05mmol)溶于盛有20ml干燥的二氯甲烷的50ml烧瓶中，常温条件下搅拌24h，TLC追踪反应进度。粗产品由氢溴酸中和后由NaBr的饱和溶液洗涤至中性，二氯甲烷萃取，硫酸钠干燥有机层后旋蒸。采用柱层析分离法对产品进行分离，洗脱剂为乙酸乙酯和甲醇梯度洗脱(2:1-0:1/v/v)。收集绿色组分，蒸干溶剂后得到式三所示化合物24.5mg,收率:26％。
式三化合物的1H NMR(500MHz,CDCl3-D1)δ(ppm):1.82(m,2H),2.34-2.45(m,6H),3.64(t,4H),4.05(t,2H),6.70(s,2H),6.99-7.93(m,24H),8.50(s,2H),12.73(s,1H).LC-MS(API-ES):m/z C53H43BF2N4O6S2Calcd944.2685,found[M+H]+945.2759.
另外，通式Ⅰ所示的其它化合物按照上述的记载制备获得。
现以式二所指化合物为例说明测定过程，以下实施例中涉及到的探针化合物均为式二所指化合物：
实施例2
将制备所得式二化合物作为探针应用于水体系、模拟生理环境和细胞内进行对HNO的检测，模拟生理条件，以下各项实验均在pH＝7.4条件下进行(HEPES缓冲溶液，浓度为40mM)，探针浓度采用2μM。
上述制备所得式二化合物对H2S的光谱响应；于10ml比色管中加入2μM式二化合物，再加入40mM HEPES，然后加入10μM H2S，超纯水定容到10ml，摇匀溶液平衡10min后，将上述工作液加入荧光皿中测定荧光光谱。荧光光谱变化如图1所示。由图1所示该化合物可用于实现生物体内的H2S检测。同时，本发明实施例提供的探针与硫化氢反应后产物结构如下；
实施例3
式二化合物对硫化氢的选择性
测试液pH采用HEPES缓冲溶液控制。取多个10ml比色管，并在每个10ml比色管中加入2μM式二化合物，再加入HEPES缓冲液，然后分别加入如图2所示，待测物依次为：硫化氢、谷胱甘肽、半胱氨酸、硫代硫酸钠、亚硫酸氢钠、维生素C、硫辛酸、环氧硫蛋白、金属硫蛋白、维生素E、尿酸、组氨酸和酪氨酸。最后用超纯水定容到10ml。摇匀溶液，25℃下平衡10min后，将各个比色管中工作液分别倒入到荧光皿中测定荧光光谱。式二化合物对H2S的选择性如图2所示。并由图可知式二化合物对硫化氢具有很好的选择性，与H2S作用后，式二化合物对应的荧光增强。
以上内容是结合具体的优选实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明的保护范围。作为荧光染料是本发明新化合物的一种用途，不能认定本发明的化合物仅用于荧光染料，对于本发明所属技术领域的普通技术人员来说，在基于本发明化合物用作荧光染料的相同作用机理的考虑下，还可以做出若干简单推理，得出本发明的化合物的其他应用用途，都应当视为属于本发明的保护范围。
Claims (5)
1.一种氟硼吡咯类衍生荧光化合物，其特征在于如通式Ⅰ所示，
通式Ⅰ中：
R1为连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团；
R2为连硫邻苯二甲酸、连硒邻苯二甲酸、连碲邻苯二甲酸基团、丁基三苯基基团、N-丙基吗啉基团或C1-25的烷基链；
X为H或卤素；
Y为N或C；
Z为N或O。
2.按权利要求1所述的氟硼吡咯类衍生荧光化合物，其特征在于：所述通式Ⅰ中R1为连硫邻苯二甲酸；R2为丁基三苯基基团或N-丙基吗啉基团；X为H；Y为N；Z为O。
3.一种权利要求1所述的氟硼吡咯类化合物的应用，其特征在于：以所述通式Ⅰ所示的氟硼吡咯类化合物作为硫化氢的荧光探针。
4.一种荧光探针，其特征在于：
荧光探针为通式Ⅰ所示的以(BODIPY)染料作为荧光母体，并在母体上引入对具备线粒体、溶酶体、内质网定位功能团的季磷盐、吗啉、C1-25烷基碳链、连硫邻苯二甲酸、连硒邻苯二甲酸或连碲邻苯二甲酸基团。
5.按权利要求4所述的荧光探针，其特征在于：所述荧光探针用于定性/定量的检测生理环境下、细胞或生物体内的硫化氢。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410173946.8A CN105017297B (zh) | 2014-04-28 | 2014-04-28 | 一种氟硼吡咯类衍生荧光化合物及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410173946.8A CN105017297B (zh) | 2014-04-28 | 2014-04-28 | 一种氟硼吡咯类衍生荧光化合物及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105017297A true CN105017297A (zh) | 2015-11-04 |
| CN105017297B CN105017297B (zh) | 2017-02-15 |
Family
ID=54407643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410173946.8A Expired - Fee Related CN105017297B (zh) | 2014-04-28 | 2014-04-28 | 一种氟硼吡咯类衍生荧光化合物及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105017297B (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106432315A (zh) * | 2016-10-17 | 2017-02-22 | 湘潭大学 | 一种基于氟硼吡咯的Cys荧光探针的制备方法和应用 |
| CN107286186A (zh) * | 2016-04-12 | 2017-10-24 | 中国科学院化学研究所 | 硫化氢荧光探针及其制备方法和应用 |
| CN116396984A (zh) * | 2022-07-21 | 2023-07-07 | 苏州炫景生物科技有限公司 | 核酸递送载体及功能协同的药物组合物应用 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558875A (zh) * | 2018-05-24 | 2018-09-21 | 泰山医学院 | 一种能够检测硫化氢的小分子荧光探针及其应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1944540A (zh) * | 2006-09-15 | 2007-04-11 | 大连理工大学 | 生物分析用近红外氟化硼络合二吡咯甲川类荧光染料 |
| CN103351335A (zh) * | 2013-05-28 | 2013-10-16 | 中南大学 | 一种荧光增强检测含巯基氨基酸的荧光分子探针的合成及应用 |
-
2014
- 2014-04-28 CN CN201410173946.8A patent/CN105017297B/zh not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1944540A (zh) * | 2006-09-15 | 2007-04-11 | 大连理工大学 | 生物分析用近红外氟化硼络合二吡咯甲川类荧光染料 |
| CN103351335A (zh) * | 2013-05-28 | 2013-10-16 | 中南大学 | 一种荧光增强检测含巯基氨基酸的荧光分子探针的合成及应用 |
Non-Patent Citations (3)
| Title |
|---|
| BO PENG等: "Fluorescent Probes Based on Nucleophilic Substitution–Cyclization for Hydrogen Sulfide Detection and Bioimaging", 《CHEM. EUR. J.》 * |
| HAIBO YU等: "A Lysosome-Targetable and Two-Photon Fluorescent Probe for Monitoring Endogenous and Exogenous Nitric Oxide in Living Cells", 《J. AM. CHEM. SOC.》 * |
| 张健: "新型羧基BODIPY及基于BODIPY的近红外荧光探针的设计、合成与应用", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107286186A (zh) * | 2016-04-12 | 2017-10-24 | 中国科学院化学研究所 | 硫化氢荧光探针及其制备方法和应用 |
| CN106432315A (zh) * | 2016-10-17 | 2017-02-22 | 湘潭大学 | 一种基于氟硼吡咯的Cys荧光探针的制备方法和应用 |
| CN106432315B (zh) * | 2016-10-17 | 2018-05-08 | 湘潭大学 | 一种基于氟硼吡咯的Cys荧光探针的制备方法和应用 |
| CN116396984A (zh) * | 2022-07-21 | 2023-07-07 | 苏州炫景生物科技有限公司 | 核酸递送载体及功能协同的药物组合物应用 |
| CN116396984B (zh) * | 2022-07-21 | 2024-02-13 | 苏州炫景生物科技有限公司 | 核酸递送载体及功能协同的药物组合物应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105017297B (zh) | 2017-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105001857B (zh) | 用于测定超氧阴离子和多硫化氢的荧光团衍生物及其应用 | |
| CN107188876B (zh) | 一种用于检测多硫化氢的近红外荧光探针的合成及应用 | |
| Wu et al. | An ICT lighten ratiometric and NIR fluorogenic probe to visualize endogenous/exogenous hydrogen sulphide and imaging in mice | |
| CN105017297A (zh) | 一种氟硼吡咯类衍生荧光化合物及其应用 | |
| CN104357044B (zh) | 一种荧光探针及其制备方法和应用 | |
| CN107602498B (zh) | 一种荧光探针及其制备方法与在酪氨酸酶检测中的应用 | |
| CN104804029A (zh) | 一种氟硼吡咯类化合物及其应用 | |
| Zhu et al. | Novel BODIPY-based fluorescent probes with large Stokes shift for imaging hydrogen sulfide | |
| CN105017128A (zh) | 一种花菁类化合物及其应用 | |
| Kumar et al. | A benzothiazolinic spiropyran for highly selective, sensitive and visible light controlled detection of copper ions in aqueous solution | |
| Chen et al. | A novel fluorescent probe with red emission and a large Stokes shift for selective imaging of endogenous cysteine in living cells | |
| Mittapelli et al. | A turn-on fluorescent GFP chromophore analog for highly selective and efficient detection of H2S in aqueous and in living cells | |
| CN107915680B (zh) | 基于四苯乙烯的atp荧光探针及其制备方法和应用 | |
| CN103864829B (zh) | 水溶性三芳基硼化合物及其制备方法和应用 | |
| Fang et al. | A novel near infrared probe with large Stokes shift for detection of H2S in living cells | |
| CN112939963B (zh) | 一种苯并吡喃酸酯衍生物及其合成方法和应用 | |
| CN107474044A (zh) | 一种香豆素类衍生物、其制备方法和应用及一种亚硫酸氢根检测试剂盒 | |
| CN110092771A (zh) | 一种用于人血清白蛋白检测的荧光探针及其制备方法、荧光试剂盒 | |
| CN104910060A (zh) | 一种荧光团衍生物及其应用 | |
| CN105017298B (zh) | 一种氟硼吡咯类化合物及其应用 | |
| CN111548304B (zh) | 一种基于三苯胺的衍生物及制备方法与应用 | |
| CN105001250A (zh) | 用于测定多硫化半胱氨酸氟硼吡咯类荧光团衍生物及其应用 | |
| Yang et al. | Solvent-dependent tautomeric equilibrium between fluorescent colorimetric probes with dual mitochondrial/liposome targetability | |
| CN109503634B (zh) | 一种异恶唑衍生物及其合成方法和检测硫化氢的应用 | |
| CN104311504B (zh) | 一种环烷基单取代氨基萤光素化合物及其制备方法与应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170215 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |