CN113135963B - Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof - Google Patents
Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof Download PDFInfo
- Publication number
- CN113135963B CN113135963B CN202110283206.XA CN202110283206A CN113135963B CN 113135963 B CN113135963 B CN 113135963B CN 202110283206 A CN202110283206 A CN 202110283206A CN 113135963 B CN113135963 B CN 113135963B
- Authority
- CN
- China
- Prior art keywords
- rare earth
- compound
- earth complex
- fluorescent dye
- complex fluorescent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229910052761 rare earth metal Inorganic materials 0.000 title claims abstract description 137
- 150000002910 rare earth metals Chemical class 0.000 title claims abstract description 128
- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 95
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000003446 ligand Substances 0.000 claims abstract description 27
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 22
- -1 rare earth ion Chemical class 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 54
- 239000002202 Polyethylene glycol Substances 0.000 claims description 51
- 150000003904 phospholipids Chemical class 0.000 claims description 51
- 229920001223 polyethylene glycol Polymers 0.000 claims description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 48
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 30
- 210000004027 cell Anatomy 0.000 claims description 26
- 229940098773 bovine serum albumin Drugs 0.000 claims description 24
- 239000002872 contrast media Substances 0.000 claims description 23
- 238000001816 cooling Methods 0.000 claims description 23
- 238000003786 synthesis reaction Methods 0.000 claims description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 20
- 230000015572 biosynthetic process Effects 0.000 claims description 20
- 238000004440 column chromatography Methods 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 19
- 239000012074 organic phase Substances 0.000 claims description 19
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 229940125904 compound 1 Drugs 0.000 claims description 16
- 229940125782 compound 2 Drugs 0.000 claims description 16
- 238000000108 ultra-filtration Methods 0.000 claims description 16
- 238000003384 imaging method Methods 0.000 claims description 15
- 229940126214 compound 3 Drugs 0.000 claims description 13
- 239000008055 phosphate buffer solution Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 159000000000 sodium salts Chemical class 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 238000009210 therapy by ultrasound Methods 0.000 claims description 8
- JHFPQYFEJICGKC-UHFFFAOYSA-N erbium(3+) Chemical compound [Er+3] JHFPQYFEJICGKC-UHFFFAOYSA-N 0.000 claims description 6
- 210000002751 lymph Anatomy 0.000 claims description 6
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 5
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 5
- 239000007983 Tris buffer Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002390 rotary evaporation Methods 0.000 claims description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 2
- 229960002317 succinimide Drugs 0.000 claims description 2
- PEHLCCGXTLWMRW-UHFFFAOYSA-N bis-lactone Chemical compound C1CC2OC(=O)C3C1OC(=O)C32 PEHLCCGXTLWMRW-UHFFFAOYSA-N 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Natural products C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 9
- 230000008033 biological extinction Effects 0.000 abstract description 7
- 229910052684 Cerium Inorganic materials 0.000 abstract description 3
- 229910052769 Ytterbium Inorganic materials 0.000 abstract description 3
- 238000006073 displacement reaction Methods 0.000 abstract description 3
- DSJXIQQMORJERS-AGGZHOMASA-M bacteriochlorophyll a Chemical class C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC([C@H](CC)[C@H]3C)=[N+]4C3=CC3=C(C(C)=O)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 DSJXIQQMORJERS-AGGZHOMASA-M 0.000 abstract description 2
- 238000012984 biological imaging Methods 0.000 abstract description 2
- 238000004891 communication Methods 0.000 abstract description 2
- 239000013307 optical fiber Substances 0.000 abstract description 2
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 abstract description 2
- 238000001228 spectrum Methods 0.000 abstract description 2
- 239000000693 micelle Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 25
- 239000000975 dye Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000003960 organic solvent Substances 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- 230000005284 excitation Effects 0.000 description 16
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 13
- 239000002953 phosphate buffered saline Substances 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 10
- 229960001701 chloroform Drugs 0.000 description 10
- 239000002105 nanoparticle Substances 0.000 description 10
- 229910052691 Erbium Inorganic materials 0.000 description 9
- 210000004204 blood vessel Anatomy 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 8
- 210000003462 vein Anatomy 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 230000001678 irradiating effect Effects 0.000 description 5
- 230000000149 penetrating effect Effects 0.000 description 5
- RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 description 4
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 210000002249 digestive system Anatomy 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- 210000004324 lymphatic system Anatomy 0.000 description 4
- 238000006862 quantum yield reaction Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000001926 lymphatic effect Effects 0.000 description 3
- 210000001365 lymphatic vessel Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 229940094989 trimethylsilane Drugs 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000000090 biomarker Substances 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
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—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
- A61K49/0036—Porphyrins
-
- 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
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/08—Preparation from other phthalocyanine compounds, e.g. cobaltphthalocyanineamine complex
- C09B47/12—Obtaining compounds having alkyl radicals, or alkyl radicals substituted by hetero atoms, bound to the phthalocyanine skeleton
- C09B47/14—Obtaining compounds having alkyl radicals, or alkyl radicals substituted by hetero atoms, bound to the phthalocyanine skeleton having alkyl radicals substituted by halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/08—Preparation from other phthalocyanine compounds, e.g. cobaltphthalocyanineamine complex
- C09B47/18—Obtaining compounds having oxygen atoms directly bound to the phthalocyanine skeleton
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- 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
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1074—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms
-
- 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
- C09K2211/1074—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms
- C09K2211/1077—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms with oxygen
-
- 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
- C09K2211/18—Metal complexes
- C09K2211/182—Metal complexes of the rare earth metals, i.e. Sc, Y or lanthanide
-
- 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
- C09K2211/18—Metal complexes
- C09K2211/187—Metal complexes of the iron group metals, i.e. Fe, Co or Ni
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Materials Engineering (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a near-infrared second window emission rare earth complex fluorescent dye and a preparation method and application thereof. The rare earth complex consists of a pyrrole macrocyclic ligand A, a rare earth ion Ln and a deuterated or halogenated tripod ligand L; a is a bacteriochlorophyll derivative, phthalocyanine or pyrrole, ln is selected from Ce, pm, eu, gd, tb, pr, nd, sm, dy, ho, er, tm and Yb, L is a deuterated or halogenated Kl ӓ ui tripod ligand and/or a deuterated or halogenated Tp tripod ligand. The rare earth complex has near-infrared absorption larger than 700nm and near-infrared second window emission larger than 1500nm, large molar extinction coefficient, narrow spectrum peak and adjustable range, stokes displacement larger than 700nm, good solubility and high quantum efficiency in various solvents, and has application prospect in the fields of biological imaging, optical fiber communication, near-infrared organic light-emitting diodes and the like.
Description
Technical Field
The invention belongs to the technical field of biological materials, and particularly relates to a rare earth complex fluorescent dye emitted by a near-infrared second window, a preparation method of the rare earth complex fluorescent dye, and application of the fluorescent dye in preparation of a contrast agent for lymph imaging and multiple detection.
Background
The fluorescent multiple coding technology can report the activities of different biomarkers in real time and is an important tool in life activities and medical health research. Compared with the wave band (400 nm-900 nm) used by the traditional fluorescence imaging, in the near-infrared second window (1000-1700 nm), especially the b region (1500 nm-1700 nm) of the near-infrared second window, the autofluorescence of the biological tissue and the scattering of light are reduced to the minimum, the imaging quality is obviously improved, and the fluorescence imaging is improved in the aspects of detection depth and resolution. Therefore, fluorescence multiple encoding is carried out in the near-infrared second window, and in-situ imaging and detection with higher resolution and signal-to-noise ratio in a living body are expected to be realized. Currently, the commonly used near-infrared second window contrast agents include some organic small molecules and quantum dots. Their stokes shift is small and the overlap of fluorescence spectra is severe, greatly limiting the number of near-infrared second window fluorescence codes. Therefore, the designed light stability is good, the absorption emission half-peak width is narrow, the Stokes displacement is large, and the emission wavelength is long and is the focus of the current near-infrared second window multiple coding fluorophore.
Disclosure of Invention
The invention aims to provide a molecular fluorescent dye emitted in a near-infrared second window b region, which has the advantages of good biocompatibility, high light stability, large Stokes shift, narrow absorption and emission half-peak width and excellent fluorescence performance, and a preparation method and application thereof.
The molecular fluorescent dye emitted by a near-infrared second window b area provided by the invention is a rare earth complex fluorescent dye, consists of a pyrrole macrocyclic ligand (marked as A), rare earth ions (marked as Ln) and a deuterated or halogenated tripod ligand (marked as L), and has a structural general formula shown as the following formula:
wherein, the pyrrole macrocyclic ligand A is bacteriochlorophyll derivative, phthalocyanine or pyrrole, the rare earth ion Ln is selected from one or more of Ce, pm, eu, gd, tb, pr, nd, sm, dy, ho, er, tm and Yb, and the deuterated or halogenated tripod ligand L is deuterated or halogenated
A tripod ligand and/or a deuterated or halogenated Tp tripod ligand.
The rare earth complex has near-infrared absorption larger than 700nm and near-infrared second window emission larger than 1500nm, large molar extinction coefficient, narrow spectrum peak (half peak width about 20 nm) and adjustable range, stokes displacement larger than 700nm, good solubility and higher quantum efficiency in various solvents, is not easy to be quenched by the influence of protic solvent environment, and has huge application prospect in the fields of biological imaging, optical fiber communication, near-infrared organic light-emitting diodes and the like.
In the present invention, the pyrrole macrocyclic ligand a is preferably a porphyrin having the following general formula I, II, III, IV:
wherein R is 1 、R 2 、R 3 、R 4 Is an aromatic ring, G 1 、G 2 、G 3 、G 4 、G 5 、G 6 、G 7 、G 8 Is one of hydrogen, alkyl, alkoxy or hydroxyl, X 1 、X 2 、X 3 、X 4 Is one of hydrogen, deuterium, fluorine, chlorine, bromine, iodine, carboxylic ester, benzene ring and alkyl.
In the present invention, R 1 、R 2 、R 3 、R 4 The aromatic ring is preferably any of the following structures:
in the present invention, G 1 、G 2 、G 3 、G 4 、G 5 、G 6 、G 7 、G 8 Preferably H, CH 3 、CH 2 CH 3 、OH、OCH 3 Or OCH 2 CH 3 One kind of (1).
In the present invention, X 1 、X 2 、X 3 、X 4 Preferably H, D, F, cl, br, I, CH 3 、CH 2 CH 3 、COOCH 2 CH 3 、 C 6 H 6 One kind of (1).
In the present invention, the pyrrole macrocyclic ligand a is more preferably selected from any one of the following:
in the present invention, the deuterated or halogenated tripod ligand L is preferably represented by one of the following structural formulas:
in the present invention, the structure of the organic complex is selected from any one or more of the following structures:
the preparation method of the rare earth complex fluorescent dye provided by the invention comprises the following specific steps:
(1) Under the condition of non-oxidizing inert atmosphere, pyrrole macrocyclic ligand A and rare earth salt react in a first organic solvent at the temperature of 60-300 ℃ to obtain an intermediate product;
(2) Reacting the intermediate product with a deuterated or halogenated tripod ligand L in a second organic solvent to obtain a rare earth complex intermediate product;
(3) And reducing the intermediate product in a third organic solvent at-78-0 ℃ to obtain the rare earth complex.
Wherein the structural general formula of the rare earth salt is LnB 3 Wherein, the rare earth ion Ln is any one of Ce, pm, eu, gd, tb, pr, nd, sm, dy, ho, er, tm and Yb, and the anion B is Cl - 、NO 3 - 、CH 3 COO - 、CF 3 COO - 、 CF 3 SO 3 - 、
Any one of them.
The first organic solvent is selected from one or more of trichlorobenzene, decahydronaphthalene, dimethyl sulfoxide, o-dichlorobenzene, diethylene glycol dimethyl ether, tetrahydrofuran, n-hexanol and toluene, preferably from one or more of trichlorobenzene, diethylene glycol dimethyl ether, tetrahydrofuran, decahydronaphthalene, dimethyl sulfoxide and toluene;
the non-oxidizing inert atmosphere is nitrogen, argon, helium, hydrogen or a nitrogen-hydrogen mixed gas, preferably nitrogen and argon;
the second organic solvent is selected from any one or more of chloroform, acetone, dimethyl sulfoxide, tetrahydrofuran, o-dichlorobenzene, methanol and toluene, preferably from any one or more of chloroform, acetone, tetrahydrofuran and dimethyl sulfoxide;
the third organic solvent is selected from any one or more of chloroform, acetone, dimethyl sulfoxide, tetrahydrofuran, methanol and toluene, preferably from any one or more of chloroform, acetone, tetrahydrofuran and dimethyl sulfoxide.
Typically, the rare earth complex fluorescent dye has a structural general formula (1) and a structural general formula (2); wherein:
the chemical synthesis route of the rare earth complex fluorescent dye with the structural general formula (1) is as follows:
the method comprises the following specific steps:
(1) Synthesis of intermediate 1
Anhydrous and oxygen-free operation, dissolving pyrrole macrocyclic ligand (compound 1) and rare earth salt (compound 2) in a first organic solvent, and carrying out reflux reaction for 12-24 hours at 60-300 ℃; centrifuging for 1000-5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1, the compound 2 and the first organic solvent is 1 (3-10) to (10-15); the first organic solvent is preferably trichlorobenzene, diethylene glycol dimethyl ether, tetrahydrofuran, decalin, dimethyl sulfoxide and toluene.
(2) Synthesis of rare earth complexes
Dissolving the intermediate 1 and the tripod ligand L (compound 3) in a second organic solvent, and reacting for 4-12 hours at 25-80 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex (general formula I); wherein the feeding molar ratio of the intermediate 1 to the compound 3 to the second organic solvent is 1 (1-5) to 10-15; the second organic solvent is preferably chloroform, acetone, tetrahydrofuran, dimethyl sulfoxide.
The chemical synthesis route of the rare earth complex fluorescent dye general structural formula (2) is as follows:
the method comprises the following specific steps:
(1) Synthesis of intermediate 1
Anhydrous and oxygen-free operation, dissolving pyrrole macrocyclic ligand (compound 1) and rare earth salt (compound 2) in a first organic solvent, and carrying out reflux reaction for 12-24 hours at 60-300 ℃; centrifuging for 1000-5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the first organic solvent is 1 (3-10) to 10-15; the first organic solvent is preferably trichlorobenzene, diethylene glycol dimethyl ether, tetrahydrofuran, decalin, dimethyl sulfoxide and toluene.
(2) Synthesis of intermediate 2
Dissolving the intermediate 1 and the tripod ligand L (compound 3) in a second organic solvent, and reacting for 4-12 hours at 25-80 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain intermediate 2; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the second organic solvent is 1 (3-10) to 10-15; the second organic solvent is preferably chloroform, acetone, tetrahydrofuran, dimethyl sulfoxide.
(3) Synthesis of rare earth complexes
Dissolving the intermediate 2 and a reducing agent (compound 4) in a third organic solvent, and reacting for 0.5-4 hours at-78-0 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex (general formula II); wherein the feeding molar ratio of the intermediate 1, the compound 4 and the third organic solvent is 1 (1-4) to 10-15; the third organic solvent is preferably chloroform, acetone, tetrahydrofuran, or dimethyl sulfoxide.
The invention also provides the application of the near-infrared second window emission rare earth complex, including the application in preparing a contrast agent for lymph imaging/blood vessel imaging and multiple detection, and the application in preparing a cell-labeled contrast agent.
The application of the rare earth complex emitted by the near-infrared second window in preparing a lymph imaging/blood vessel imaging and multi-detection contrast agent comprises the following specific steps:
dissolving a rare earth complex fluorescent dye (for example, 1a, prepared in example 1) and phospholipid polyethylene glycol (2000) in chloroform, stirring for 0.5-1 hour, performing rotary evaporation to remove a solvent, performing vacuum drying, heating to 40-80 ℃, adding into Phosphate Buffered Saline (PBS) at 40-80 ℃ for dissolution, performing ultrasonic treatment, cooling to room temperature, and performing ultrafiltration concentration by using an ultrafiltration tube with 30KD to obtain a final contrast agent; wherein the mass percentage of the rare earth complex fluorescent dye and the phospholipid polyethylene glycol (2000) is (1), (500-50)), and the final concentration of the contrast agent is 0.01-1 mM.
The micelle can be used as a contrast agent for imaging blood vessels of the whole body of a mouse, imaging lymphatic drainage of legs, multiple markers of blood circulation and lymphatic system of the mouse, and multiple marker detection imaging of digestive system, blood circulation system and the like.
The application of the rare earth complex emitted by the near-infrared second window in the preparation of the cell-labeled contrast agent comprises the following specific steps:
adding 4- (N-maleimide methyl) cyclohexane-1-carboxylic acid sulfonic group succinimide ester sodium salt into dimethyl sulfoxide solution of cell penetrating peptide (RKKRRQRRRC), and stirring for 0.5-4 hours at room temperature; then adding the mixture into Phosphate Buffered Saline (PBS) of Bovine Serum Albumin (BSA), and stirring the mixture for 1 to 8 hours at room temperature; then adding rare earth complex fluorescent dye (such as 1a, prepared in example 1), performing ultrasonic treatment, and performing ultrafiltration concentration through an ultrafiltration tube with 30KD to obtain the final contrast agent. Wherein the molar ratio of the rare earth complex fluorescent dye to Bovine Serum Albumin (BSA) is (1-5)), and the final concentration of the contrast agent is 10-25. Mu.M.
The complex can mark and light the cell, and the cell can be tracked. And observing the metastasis path of the cancer cells in the mice.
The rare earth complex fluorescent dye provided by the invention has the advantages of large molar extinction coefficient, long absorption and emission wavelength, narrow half-peak width and adjustable wavelength. The fluorescent dye is not easy to cause color change due to solvation in a polar solvent, and has more excellent light stability and brighter fluorescence intensity in water compared with the existing common near-infrared fluorescent dye in the second window b area, so that high-resolution imaging of lymphatic vessels and blood vessels of a mouse, multiple labeling of blood circulation and lymphatic system of the mouse, multiple labeling detection imaging of digestive system and blood circulation system and the like can be realized. The rare earth complex fluorescent dye is emitted in a near infrared second window b area, so that in-vivo cell tracking microscopic imaging with high resolution and high signal-to-noise ratio and deeper tissue penetration depth can be realized.
The rare earth complex fluorescent dye (1 a, shown below) has a maximum absorption peak at 766nm and a maximum emission peak at 1532nm in a dichloromethane solution.
The rare earth complex fluorescent dye (1 a, shown as the following) has a molar extinction coefficient of 113000M in a dichloromethane solution -1 cm -1 。
The rare earth complex fluorescent dye (1 a, as shown below) of the present invention has an absolute fluorescence quantum yield of 0.0138% in a dichloromethane solution.
The micelle formed by the rare earth complex fluorescent dye (1 a, shown as the following) and phospholipid polyethylene glycol 2000 has the maximum absorption peak at 768nm and the maximum emission peak at 1532nm in a phosphate buffer solution.
The micelle formed by the rare earth complex fluorescent dye (1 a, shown as the following) and phospholipid polyethylene glycol 2000 has a molar extinction coefficient of 108000M in phosphate buffer solution -1 cm -1 。
The absolute fluorescence quantum yield of the micelle formed by the rare earth complex fluorescent dye (1 a, shown as the following) and phospholipid polyethylene glycol 2000 in a phosphate buffer solution is 0.0104%.
The micelle formed by the rare earth complex fluorescent dye (1 a, shown as the following) and phospholipid polyethylene glycol 2000 and the rare earth nano-particles doped with erbium ions respectively emit fluorescence of 1450-1650nm under the excitation of 760nm and 980nm in aqueous solution.
The micelle formed by the rare earth complex fluorescent dye (1 a, shown as the following) and phospholipid polyethylene glycol 2000 and the micelle formed by the Cy7.5 dye and the phospholipid polyethylene glycol 2000 can emit fluorescence in the range of 1450-1650nm and fluorescence in the range of 1000-1400nm under the excitation of 760nm in aqueous solution.
The rare earth complex fluorescent dye (1 a, shown as the following) and a cell penetrating peptide-bovine serum albumin complex emit fluorescence in the range of 1450-1650nm under the excitation of 760nm in aqueous solution.
The rare earth complex fluorescent dye (2 a, shown as the following text) has the maximum absorption peak at 742nm and the maximum emission peak at 1532nm in a dichloromethane solution.
The rare earth complex fluorescent dye (2 a, shown below) of the invention has a molar extinction coefficient of 69000M in a dichloromethane solution -1 cm -1 。
The rare earth complex fluorescent dye (2 a, as shown below) of the present invention has an absolute fluorescence quantum yield of 0.0112% in a dichloromethane solution.
The micelle formed by the rare earth complex fluorescent dye (2 a, shown as the following) and phospholipid polyethylene glycol 2000 has a maximum absorption peak at 750nm and a maximum emission peak at 1532nm in a phosphate buffer solution.
The micelle formed by the rare earth complex fluorescent dye (2 a, shown as the following) and phospholipid polyethylene glycol 2000 has a molar extinction coefficient of 36000M in a phosphate buffer solution -1 cm -1 。
The absolute fluorescence quantum yield of the micelle formed by the rare earth complex fluorescent dye (2 a, shown as the following) and the phospholipid polyethylene glycol 2000 in the phosphate buffer solution is 0.0082%.
The micelle formed by the rare earth complex fluorescent dye (2 a, shown as the following) and phospholipid polyethylene glycol 2000 and the rare earth nano-particles doped with erbium ions respectively emit fluorescence of 1450-1650nm under the excitation of 730nm and 980nm in aqueous solution.
The micelle formed by the rare earth complex fluorescent dye (2 a, shown as the following) and phospholipid polyethylene glycol 2000 and the micelle formed by the Cy7.5 dye and the phospholipid polyethylene glycol 2000 can emit fluorescence in the range of 1450-1650nm and fluorescence in the range of 1000-1400nm under the excitation of 730nm in aqueous solution.
The rare earth complex fluorescent dye (2 a, shown below) and a cell penetrating peptide-bovine serum albumin complex emit fluorescence in the range of 1450-1650nm under the excitation of 730nm in aqueous solution.
Drawings
FIG. 1 shows an absorption spectrum of a rare earth complex fluorescent dye (1 a, shown below) in dichloromethane.
FIG. 2 shows fluorescence emission spectra of rare earth complex fluorescent dye (1 a, shown below) in dichloromethane and phosphate buffered saline solution.
FIG. 3 is an image of mouse leg lymphatic drainage by micelles formed by a rare earth complex fluorescent dye (1 a, as shown below) and phospholipid polyethylene glycol 2000.
FIG. 4 shows the imaging of the micelles formed by the rare earth complex fluorescent dye (1 a, as shown below) and phospholipid polyethylene glycol 2000 on the brain and leg vessels of mice.
Fig. 5 is an image of a micelle formed by the rare earth complex fluorescent dye (1 a, shown below) and phospholipid polyethylene glycol 2000 and a micelle formed by the rare earth nanoparticle doped with erbium ions and phospholipid polyethylene glycol 2000, which respectively emit fluorescence spectra of 1450-1650nm under the excitation of 760nm and 980nm in an aqueous solution, and an image of a micelle formed by the rare earth complex fluorescent dye (1 a, shown below) and phospholipid polyethylene glycol 2000 and a micelle formed by the rare earth nanoparticle doped with erbium ions and phospholipid polyethylene glycol 2000, which respectively illuminate lymphatic vessels and blood vessels of a mouse under the excitation light sources of the micelles.
FIG. 6 is an image of the micelle of rare earth complex fluorescent dye (1 a, as shown below) and phospholipid polyethylene glycol 2000 and the micelle of Cy7.5 dye and phospholipid polyethylene glycol 2000 emitting fluorescence in the range of 1450-1650nm and 1000-1400nm under 760nm excitation in aqueous solution, and the image of the micelle of rare earth complex fluorescent dye (1 a, as shown below) and phospholipid polyethylene glycol 2000 and the micelle of Cy7.5 dye and phospholipid polyethylene glycol 2000 respectively illuminating the liver and the intestinal tract under 760nm excitation.
FIG. 7 is an image of the complex of the rare earth complex fluorescent dye (1 a, as shown below) and bovine serum albumin and the micelle of Cy7.5 dye and phospholipid polyethylene glycol 2000, which respectively illuminate cells and cerebral vessels under 760nm excitation.
Fig. 8 is a graph showing absorption and emission spectra of the rare earth complex-based fluorescent dye (2 a, shown below) in dichloromethane.
Fig. 9 is an image of mouse leg lymphatic drainage by micelles formed by rare earth complex fluorescent dye (2 a, as shown below) and phospholipid polyethylene glycol 2000.
Fig. 10 is an image of the mouse leg and brain vessels formed by micelles of the rare earth complex fluorescent dye (2 a, as shown below) and phospholipid polyethylene glycol 2000.
Fig. 11 is an image of a micelle formed by the rare earth complex fluorescent dye (2 a, shown below) and phospholipid polyethylene glycol 2000 and a micelle formed by the rare earth nanoparticle doped with erbium ion and phospholipid polyethylene glycol 2000, which respectively emit fluorescence spectra of 1450-1650nm under the excitation of 730nm and 980nm in aqueous solution, and an image of a micelle formed by the rare earth complex fluorescent dye (2 a, shown below) and phospholipid polyethylene glycol 2000 and a micelle formed by the rare earth nanoparticle doped with erbium ion and phospholipid polyethylene glycol 2000, which respectively illuminate lymphatic vessels and blood vessels of a mouse under the excitation light sources of the two.
FIG. 12 is an image of the micelle of rare earth complex fluorescent dye (2 a, as shown below) with phospholipid polyethylene glycol 2000 and the micelle of Cy7.5 dye with phospholipid polyethylene glycol 2000 emitting fluorescence in the range of 1450-1650nm and fluorescence in the range of 1000-1400nm under the excitation of 730nm in aqueous solution, and the image of the micelle of rare earth complex fluorescent dye (2 a, as shown below) with phospholipid polyethylene glycol 2000 and the image of the micelle of Cy7.5 dye with phospholipid polyethylene glycol 2000 respectively illuminating the liver and the intestine under the excitation of 730 nm.
FIG. 13 is an image of the complex of a rare earth complex fluorescent dye (2 a, as shown below) and bovine serum albumin and the micelle of Cy7.5 dye and phospholipid polyethylene glycol 2000, which respectively illuminate cells and cerebral vessels under 730nm excitation.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described with the following embodiments, but the present invention is by no means limited to these examples. The following description is only a preferred embodiment of the present invention, and is only for the purpose of explaining the present invention, and should not be construed as limiting the scope of the present invention. It should be understood that any modification, substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Example 1:
the preparation of the rare earth complex fluorescent dye 1a has the following structural formula:
the specific synthetic route is as follows:
the method comprises the following specific steps:
(1) Synthesis of intermediate 1
Carrying out anhydrous and oxygen-free operation, dissolving bis-reduced pentafluotetraphenylporphyrin (compound 1) and tris [ N, N-bis (trimethylsilane) amine ] erbium (III) (compound 2) in toluene, and carrying out reflux reaction at 110 ℃ for 24 hours; centrifuging at 5000 rpm twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of rare earth complexes
The intermediate 1,
Dissolving tripod ligand sodium salt (compound 3) in tetrahydrofuran solvent, and reacting at 80 ℃ for 8 hours; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex 1a; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1.
Example 2:
the preparation of the rare earth complex fluorescent dye 2a has the following structural formula:
the specific synthetic route is as follows:
the method comprises the following specific steps:
(1) Synthesis of intermediate 1
Anhydrous and oxygen-free operation, dissolving the dilactone pentafluor tetraphenyl porphyrin (compound 1) and the tri [ N, N-bis (trimethyl silane) amine ] erbium (III) (compound 2) in toluene, and carrying out reflux reaction for 24 hours at 110 ℃; centrifuging for 5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of intermediate 2
The intermediate 1,
Dissolving tripod ligand sodium salt (compound 3) in tetrahydrofuran solvent, and reacting at 80 ℃ for 8 hours; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain intermediate 2; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1.
(3) Synthesis of rare earth complexes
Dissolving the intermediate 2 and DIBAL-H (compound 4) in tetrahydrofuran solution, and reacting at-78 ℃ for 1 hour; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex (2 a); wherein the feeding molar ratio of the intermediate 1, the compound 4 and the tetrahydrofuran is 1.
Example 3:
the preparation of the rare earth complex fluorescent dye 3a has the following structural formula:
the specific synthetic route is as follows:
the method comprises the following specific steps:
(1) Synthesis of intermediate 1
Carrying out anhydrous and oxygen-free operation, dissolving bis-reduced pentafluotetraphenylporphyrin (compound 1) and tris [ N, N-bis (trimethylsilane) amine ] erbium (III) (compound 2) in toluene, and carrying out reflux reaction at 110 ℃ for 24 hours; centrifuging for 5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of rare earth complexes
Dissolving the intermediate 1 and Tp tripod ligand sodium salt (compound 3) in a tetrahydrofuran solvent, and reacting at 80 ℃ for 8 hours; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex (3 a); wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1.
Example 4:
the preparation method of the micelle formed by the rare earth complex fluorescent dye and phospholipid polyethylene glycol takes the rare earth complex fluorescent dye 1a and DOPE-PEG2000 as examples. The method comprises the following specific steps:
dissolving 1.6mg of rare earth complex fluorescent dye 1a and 160mg of DOPE-PEG2000 in 20mL of trichloromethane, stirring for 1 hour, performing rotary evaporation to remove the solvent, performing vacuum drying, heating to 80 ℃, adding 20mL of Phosphate Buffered Saline (PBS) at 80 ℃, dissolving, performing ultrasonic treatment, cooling to room temperature, and performing ultrafiltration concentration through an ultrafiltration tube with the volume of 30KD to obtain a final contrast agent; wherein, the mass percentage of the rare earth complex fluorescent dye and the DOPE-PEG2000 is (1.
The application example is as follows:
the rare earth complex fluorescent dye 1a and phospholipid polyethylene glycol form micelles to image the leg lymph of the mouse. The method comprises the following specific steps:
injecting 25 μ L of micelle solution with dye concentration of 1mM into anesthetized web of mouse, and irradiating right leg of mouse with 760nm external laser with power density of 55mW/cm 2 (see FIG. 3).
The micelle formed by the rare earth complex fluorescent dye 1a and phospholipid polyethylene glycol images the brain and leg blood vessels of the mouse. The method comprises the following specific steps:
feeding hempThe drunk mice were treated by tail vein injection of 200. Mu.L of a micelle solution having a dye concentration of 1mM, and the brains and legs of the mice were irradiated with 760nm external laser having a power density of 55mW/cm 2 (see fig. 4).
The micelle formed by the rare earth complex fluorescent dye 1a and phospholipid polyethylene glycol, the micelle formed by the phospholipid polyethylene glycol 2000 and the rare earth nano-particles doped with erbium ions mark the blood and lymphatic system of a mouse respectively. The method comprises the following specific steps:
injecting 25 mu L of micelle solution with the concentration of 1mM of rare earth complex dye at the web of anesthetized mice, then injecting 200 mu L of micelle solution with the concentration of 20mg/mL of erbium ion-doped rare earth nanoparticles into anesthetized mice through tail vein, and then irradiating the legs of the mice with 760nm and 980nm lasers with the power of 55mW/cm respectively 2 And 100mW/cm 2 (see fig. 5).
The micelle formed by the rare earth complex fluorescent dye 1a and phospholipid polyethylene glycol 2000 and the micelle formed by the Cy7.5 dye and the phospholipid polyethylene glycol 2000 respectively mark the blood circulation and the digestive system of a mouse. The method comprises the following specific steps:
anesthetized mice were injected via tail vein with 200 μ lcy7.5 dye concentration of 125 μ M in micellar solution; one hour later, the anesthetized mice were orally perfused with 100. Mu.L of a micellar solution of a rare earth complex dye concentration of 1mM, and the abdomen of the mice was irradiated with a 760nm external laser having a power density of 55mW/cm 2 The fluorescence of 1000-1400nm and 1400-1700nm was collected separately using a combination of 850nm long pass, 1000nm long pass, 1400nm short pass, and 850nm long pass, 1000nm long pass, and 1400nm long pass filters (see fig. 6).
Example 5:
a preparation method of a compound formed by rare earth complex fluorescent dye and cell penetrating peptide-bovine serum albumin takes rare earth complex fluorescent dye 1a and cell penetrating peptide (RKKRRQRRRC) -bovine serum albumin as an example, and comprises the following specific steps:
the sodium salt of sulfonic succinimidyl 4- (N-maleimidomethyl) cyclohexane-1-carboxylate was added to a solution of cell-penetrating peptide (RKKRRQRRRC) in dimethyl sulfoxide and stirred at room temperature for 1 hour. Then adding Phosphate Buffered Saline (PBS) of Bovine Serum Albumin (BSA), stirring for 4 hours at room temperature, then adding the rare earth complex fluorescent dye 1a, performing ultrasonic treatment, and then performing ultrafiltration concentration through an ultrafiltration tube with the voltage of 30KD to obtain the final contrast agent. Wherein, the molar ratio of the rare earth complex fluorescent dye to the Bovine Serum Albumin (BSA) is (1:1), and the final concentration of the contrast agent is 25 μ M.
Application example:
the movement of osteosarcoma cells (143 b cells) in cerebral vessels of mice is tracked by a complex formed by a rare earth complex fluorescent dye and cell penetrating peptide-bovine serum albumin.
The method comprises the following specific steps:
incubating the complex formed by the rare earth complex fluorescent dye 1a and bovine serum albumin with 143b cells for 12 hours, discarding the culture medium, washing the culture dish twice by using phosphate buffer solution, and removing the rare earth complex fluorescent dye 1a without marked cells. The cells were then re-digested and finally dispersed in a phosphate buffer (100. Mu.L approximately containing 1X 10 6 143b cells). The left ventricle of the anesthetized mice was injected with 100. Mu.L of the above solution, while the vessels were illuminated by tail vein injection of 200. Mu.L of Cy7.5 dye in 125. Mu.M micellar solution. Irradiating mouse brain with 760nm external laser with power density of 55mW/cm 2 Fluorescence at 1000-1400nm and 1400-1700nm was collected using combinations of 850nm long pass, 1000nm long pass, 1400nm short pass, and 850nm long pass, 1000nm long pass, and 1400nm long pass filters (see FIG. 7).
Example 6:
dissolving 1.6mg of rare earth complex fluorescent dye 2a and 160mg of DOPE-PEG2000 in 20mL of trichloromethane, stirring for 1 hour, performing rotary evaporation to remove the solvent, performing vacuum drying, heating to 80 ℃, adding 20mL of Phosphate Buffered Saline (PBS) at 80 ℃, dissolving, performing ultrasonic treatment, cooling to room temperature, and performing ultrafiltration concentration through an ultrafiltration tube with the volume of 30KD to obtain a final contrast agent; wherein, the mass percentage of the rare earth complex fluorescent dye and the DOPE-PEG2000 is (1.
Application example:
the rare earth complex fluorescent dye 2a and phospholipid polyethylene glycol form micelles to image the leg lymph of the mouse. The method comprises the following specific steps:
injecting 25 muL of micelle solution with dye concentration of 1mM at the web of anesthetized mouse, irradiating the right leg of the mouse by using 730nm external laser with the power density of 80mW/cm 2 (see fig. 9).
The micelle formed by the rare earth complex fluorescent dye 2a and phospholipid polyethylene glycol images the blood vessels of the legs and the brains of the mice. The method comprises the following specific steps:
anesthetized mice were injected via the tail vein with 200. Mu.L of a 1mM dye micelle solution, and the brain and legs of the mice were irradiated with a 730nm external laser at a laser power density of 80mW/cm 2 (see fig. 10).
The micelle formed by the rare earth complex fluorescent dye 2a and phospholipid polyethylene glycol, the micelle formed by the phospholipid polyethylene glycol 2000 and the rare earth nano-particles doped with erbium ions mark the blood and lymphatic system of a mouse respectively. The method comprises the following specific steps:
injecting 25 mul of micellar solution with the dye concentration of the rare earth complex being 1mM at the fin of an anesthetized mouse, then injecting 200 mul of micellar solution with the concentration of rare earth nano particles being 20mg/mL into the anesthetized mouse through the tail vein, and then respectively irradiating the leg of the mouse by using 730nm lasers and 980nm lasers with the power of 80mW/cm respectively 2 And 100mW/cm 2 (see FIG. 11).
Micelles formed by the rare earth complex fluorescent dye 2a and the phospholipid polyethylene glycol 2000 and micelles formed by the Cy7.5 dye and the phospholipid polyethylene glycol 2000 respectively mark the blood circulation and the digestive system of a mouse. The method comprises the following specific steps:
anesthetized mice were injected via tail vein with 200 μ lcy7.5 dye concentration of 125 μ M in micellar solution; one hour later, the anesthetized mice were orally perfused with 100. Mu.L of a micellar solution of a rare earth complex dye concentration of 1mM, and the abdomen of the mice was irradiated with a 730nm external laser having a power density of 80mW/cm 2 Respectively collecting 1000-1400nm and 1400-1700nm fluorescence by using 850nm long pass, 1000nm long pass, 1400nm short pass, 850nm long pass, 1000nm long pass and 1400nm long pass filter combinations (see the description in the specification ofFig. 12).
Example 7:
the sodium salt of sulfonic succinimidyl 4- (N-maleimidomethyl) cyclohexane-1-carboxylate was added to a solution of cell-penetrating peptide (RKKRRQRRRC) in dimethyl sulfoxide and stirred at room temperature for 1 hour. Then adding Phosphate Buffered Saline (PBS) of Bovine Serum Albumin (BSA), stirring for 4 hours at room temperature, then adding rare earth complex fluorescent dye 2a, performing ultrasonic treatment, and then performing ultrafiltration concentration through an ultrafiltration tube with the voltage of 30KD to obtain the final contrast agent. Wherein, the molar ratio of the rare earth complex fluorescent dye to Bovine Serum Albumin (BSA) is (1:1), and the final concentration of the contrast agent is 25 μ M.
Application example:
the movement of the osteosarcoma cells (143 b cells) marked by the complex formed by the rare earth complex fluorescent dye and the cell penetrating peptide-bovine serum albumin in the cerebral vessels of the mice is tracked.
The method comprises the following specific steps:
incubating the complex formed by the rare earth complex fluorescent dye 2a and bovine serum albumin with 143b cells for 12 hours, discarding the culture medium, washing the culture dish twice by using phosphate buffer solution, and removing the rare earth complex fluorescent dye 2a without marked cells. The cells were then re-digested and finally dispersed in a phosphate buffer (100. Mu.L approximately containing 1X 10 6 143b cells). The left ventricle of the anesthetized mice was injected with 100. Mu.L of the above solution, while the vessels were illuminated by tail vein injection of 200. Mu.L of Cy7.5 dye in 125. Mu.M micellar solution. The mouse brain was irradiated with a 730nm external laser. The power density of the laser is 80mW/cm 2 Fluorescence at 1000-1400nm and 1400-1700nm was collected using combinations of 850nm long pass, 1000nm long pass, 1400nm short pass, and 850nm long pass, 1000nm long pass, and 1400nm long pass filters (see FIG. 13).
Claims (4)
1. The rare earth complex fluorescent dye emitted by a near-infrared second window is characterized by consisting of a pyrrole macrocyclic ligand, rare earth ions and a tripod ligand; the structural formula is one of the following formulas:
2. the method of claim 1, wherein the second window of near-infrared emission is selected from the group consisting of:
the synthetic route of the rare earth complex fluorescent dye 1a is as follows:
the preparation method comprises the following specific steps:
(1) Synthesis of intermediate 1
Carrying out anhydrous and oxygen-free operation, dissolving compound 1 bis-reduced pentafluotetraphenylporphyrin and compound 2 tris [ N, N-bis (trimethylsilane) amine ] erbium (III) in toluene, and carrying out reflux reaction at 110 ℃ for 24 hours; centrifuging at 5000 rpm twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of rare earth complexes
Intermediate 1 and compound
Dissolving tripod ligand sodium salt in tetrahydrofuran solvent, and reacting for 8 hours at 80 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex 1a; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1;
the synthesis route of the rare earth complex fluorescent dye 2a is as follows:
the preparation method comprises the following specific steps:
(1) Synthesis of intermediate 1
Anhydrous and oxygen-free operation, dissolving compound 1 bis-lactone pentafluoride tetraphenylporphyrin and compound 2 tris [ N, N-bis (trimethylsilyl) amine ] erbium (III) in toluene, and carrying out reflux reaction at 110 ℃ for 24 hours; centrifuging for 5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of intermediate 2
Reacting the intermediate 1 and the compound
Dissolving tripod ligand sodium salt in tetrahydrofuran solvent, and reacting at 80 deg.C for 8 hr; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain intermediate 2; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1;
(3) Synthesis of rare earth complexes
Dissolving the intermediate 2 and the compound 4DIBAL-H in a tetrahydrofuran solution, and reacting for 1 hour at-78 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex 2a; wherein the feeding molar ratio of the intermediate 1, the compound 4 and the tetrahydrofuran is 1;
(III) the synthetic route of the rare earth complex fluorescent dye 3a is as follows:
the preparation method comprises the following specific steps:
(1) Synthesis of intermediate 1
Carrying out anhydrous and oxygen-free operation, dissolving compound 1 bis-reduced pentafluotetraphenylporphyrin and compound 2 tris [ N, N-bis (trimethylsilane) amine ] erbium (III) in toluene, and carrying out reflux reaction at 110 ℃ for 24 hours; centrifuging for 5000 r/min twice after cooling; filtering to remove solid insoluble substances, concentrating the organic phase, and separating by column chromatography under reduced pressure to obtain intermediate 1; wherein the feeding molar ratio of the compound 1 to the compound 2 to the toluene is 1;
(2) Synthesis of rare earth complexes
Dissolving the intermediate 1 and the compound 3Tp tripod ligand sodium salt in a tetrahydrofuran solvent, and reacting for 8 hours at 80 ℃; cooling to room temperature, filtering, concentrating the organic phase, and separating by column chromatography to obtain the rare earth complex 3a; wherein the feeding molar ratio of the intermediate 1, the compound 3 and the tetrahydrofuran is 1.
3. The application of the rare earth complex fluorescent dye in preparing a contrast agent for lymph imaging and multiple detection as claimed in claim 1 comprises the following specific steps:
dissolving rare earth complex fluorescent dye and phospholipid polyethylene glycol in chloroform, stirring for 0.5-1 hour, removing the solvent by rotary evaporation, drying in vacuum, heating to 40-80 ℃, adding phosphate buffer solution at 40-80 ℃ for dissolving, performing ultrasonic treatment, cooling to room temperature, and performing ultrafiltration concentration through an ultrafiltration tube with 30KD to obtain the final contrast agent; wherein the mass ratio of the rare earth complex fluorescent dye to the phospholipid polyethylene glycol is 1 (500-50), and the concentration of the final contrast agent is 0.01-1 mM.
4. The application of the rare earth complex fluorescent dye in the preparation of a cell-labeled contrast agent according to claim 1 comprises the following specific steps:
adding 4- (N-maleimide methyl) cyclohexane-1-carboxylic acid sulfo group succinimide ester sodium salt into dimethyl sulfoxide solution of cell penetrating peptide RKKRRQRRRC, stirring for 0.5-4 hours at room temperature; then adding the mixture into phosphate buffer solution of bovine serum albumin, and stirring the mixture for 1 to 8 hours at room temperature; then adding rare earth complex fluorescent dye, carrying out ultrasonic treatment, and then carrying out ultrafiltration concentration through an ultrafiltration tube with the voltage of 30KD to obtain the final contrast agent; wherein, the proportion of the rare earth complex fluorescent dye to the bovine serum albumin by mole number is 1 (1-5), and the final concentration of the contrast agent is 10-25 MuM.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110283206.XA CN113135963B (en) | 2021-03-16 | 2021-03-16 | Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110283206.XA CN113135963B (en) | 2021-03-16 | 2021-03-16 | Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113135963A CN113135963A (en) | 2021-07-20 |
| CN113135963B true CN113135963B (en) | 2022-11-18 |
Family
ID=76811360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110283206.XA Active CN113135963B (en) | 2021-03-16 | 2021-03-16 | Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113135963B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108264896B (en) * | 2016-12-30 | 2021-09-17 | 北京大学 | Luminescent material and preparation method thereof |
| CN108424430B (en) * | 2018-06-13 | 2021-03-30 | 北京大学 | Rare earth complex with near-infrared pH intensity and life response |
| CN109180638A (en) * | 2018-10-10 | 2019-01-11 | 复旦大学 | The second window of near-infrared emits Cyanine fluorochrome and its preparation method and application |
-
2021
- 2021-03-16 CN CN202110283206.XA patent/CN113135963B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113135963A (en) | 2021-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Structural modification of BODIPY: Improve its applicability | |
| Fan et al. | Mobile phone flashlight‐excited red afterglow bioimaging | |
| Zhu et al. | Anti-Stokes shift luminescent materials for bio-applications | |
| Lou et al. | Organic dots based on AIEgens for two‐photon fluorescence bioimaging | |
| Cheng et al. | Highly-sensitive multiplexed in vivo imaging using PEGylated upconversion nanoparticles | |
| CN109336909B (en) | Near-infrared two-region fluorescent compound with aggregation-induced emission property, preparation method thereof, nano-micelle and application thereof | |
| Chen et al. | Preparation and photodynamic therapy application of NaYF4: Yb, Tm–NaYF4: Yb, Er multifunctional upconverting nanoparticles | |
| CN102942933B (en) | In-water-phase monodisperse sodium yttrium tetrafluoride multi-color luminescent nanoparticle and preparation method thereof | |
| Hou et al. | Recent advances of pure organic room temperature phosphorescence materials for bioimaging applications | |
| US11957752B2 (en) | Near-infrared nano-photosensitizer, and preparation method and use thereof | |
| Lu et al. | Rare-earth doped nanoparticles with narrow NIR-II emission for optical imaging with reduced autofluorescence | |
| Bian et al. | A proton-activatable aminated-chrysophanol sensitizer for photodynamic therapy | |
| CN104231502A (en) | Dual-targeting near-infrared up-conversion nano material as well as preparation method and application thereof | |
| CN113135963B (en) | Near-infrared second window emission rare earth complex fluorescent dye and preparation method and application thereof | |
| US20240082431A1 (en) | Metallohydroporphyrins for photoacoustic imaging | |
| CN108424430B (en) | Rare earth complex with near-infrared pH intensity and life response | |
| CN107529514B (en) | Preparation method and application of fluorine ion-doped carbon dots | |
| CN114349756A (en) | AIE organic small molecule and preparation method and application thereof | |
| Zhang et al. | Enhanced brightness and electron affinity of terrylenediimide with sulfone-bridged substituents on the bay region | |
| Dai et al. | Ultralong aqueous organic room-temperature phosphorescent probes for in vivo time-resolved bioimaging | |
| CN116730904A (en) | Near infrared two-region cyanine compound and synthetic method and application thereof | |
| Mula | BODIPY: A Unique Dye for Versatile Optical Applications | |
| Sun et al. | Near-infrared materials | |
| CN111808610A (en) | Carbon nitride-like phosphorus-rich quantum dot fluorescent probe and preparation method and application thereof | |
| CN104761578A (en) | Rhodium tetraphenylporphyrin-aza-BODIPY-based near infrared absorption phosphorescence materials, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |