CN113201018A - Mn (II) complex with AIE property and living cell mitochondria targeting function and preparation method and application thereof - Google Patents
Mn (II) complex with AIE property and living cell mitochondria targeting function and preparation method and application thereof Download PDFInfo
- Publication number
- CN113201018A CN113201018A CN202110482983.7A CN202110482983A CN113201018A CN 113201018 A CN113201018 A CN 113201018A CN 202110482983 A CN202110482983 A CN 202110482983A CN 113201018 A CN113201018 A CN 113201018A
- Authority
- CN
- China
- Prior art keywords
- complex
- mncl
- photon
- function
- aie
- 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
- 210000003470 mitochondria Anatomy 0.000 title claims abstract description 16
- 230000008685 targeting Effects 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 210000004027 cell Anatomy 0.000 claims abstract description 13
- 229910021380 Manganese Chloride Inorganic materials 0.000 claims description 30
- 239000011565 manganese chloride Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 7
- FZPXKEPZZOEPGX-UHFFFAOYSA-N n,n-dibutylaniline Chemical compound CCCCN(CCCC)C1=CC=CC=C1 FZPXKEPZZOEPGX-UHFFFAOYSA-N 0.000 claims description 7
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 claims description 6
- AJKVQEKCUACUMD-UHFFFAOYSA-N 2-Acetylpyridine Chemical compound CC(=O)C1=CC=CC=N1 AJKVQEKCUACUMD-UHFFFAOYSA-N 0.000 claims description 5
- 229910019213 POCl3 Inorganic materials 0.000 claims description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000011358 absorbing material Substances 0.000 claims description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 abstract description 35
- 230000005284 excitation Effects 0.000 abstract description 35
- 239000000463 material Substances 0.000 abstract description 11
- JFJNVIPVOCESGZ-UHFFFAOYSA-N 2,3-dipyridin-2-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CN=C1C1=CC=CC=N1 JFJNVIPVOCESGZ-UHFFFAOYSA-N 0.000 abstract description 5
- CYRGZAAAWQRSMF-UHFFFAOYSA-N aluminium selenide Chemical compound [Al+3].[Al+3].[Se-2].[Se-2].[Se-2] CYRGZAAAWQRSMF-UHFFFAOYSA-N 0.000 abstract description 2
- 238000012984 biological imaging Methods 0.000 abstract description 2
- 230000008832 photodamage Effects 0.000 abstract description 2
- 239000011572 manganese Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000002189 fluorescence spectrum Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000011161 development Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 238000004020 luminiscence type Methods 0.000 description 3
- 229940099607 manganese chloride Drugs 0.000 description 3
- 235000002867 manganese chloride Nutrition 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012788 optical film Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 238000002311 multiphoton fluorescence microscopy Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000000482 two photon fluorescence microscopy Methods 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000011365 complex material Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- IKEOZQLIVHGQLJ-UHFFFAOYSA-M mitoTracker Red Chemical group [Cl-].C1=CC(CCl)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 IKEOZQLIVHGQLJ-UHFFFAOYSA-M 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000012800 visualization Methods 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
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6402—Atomic fluorescence; Laser induced fluorescence
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
- G01N21/6458—Fluorescence microscopy
-
- 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
- C09K2211/188—Metal complexes of other metals not provided for in one of the previous groups
-
- 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
- G01N2021/6417—Spectrofluorimetric devices
- G01N2021/6419—Excitation at two or more wavelengths
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention discloses a Mn (II) complex with AIE (aluminum selenide) property and a living cell mitochondria targeting function, a preparation method and application thereof, relating to the technical field of multiphoton absorption materials, FD-MnCl for short2The structural formula is as follows:
the novel terpyridine Mn (II) complex synthesized by the invention is a multi-photon absorption material with a cell developing function, and compared with other materials, the complex has the characteristics of larger three-photon absorption cross section, low excitation energy, long wavelength, strong penetrability, small light damage and the like, can be used for multi-photon biological imaging, and has obvious application value.
Description
The technical field is as follows:
the invention relates to the technical field of multi-photon absorption materials, in particular to a Mn (II) complex with AIE (aluminum selenide) property and a living cell mitochondria targeting function, and a preparation method and application thereof.
Background art:
multiphoton absorption is a nonlinear optical effect. Under irradiation of a high intensity laser beam, it is possible for a substance to absorb several, even tens of photons simultaneously, a process known as multiphoton absorption. Compared with the traditional single photon absorption, the multiphoton absorption has obvious advantages in the fields of three-dimensional controllability, photolytic drug release, bioluminescence labeling, multiphoton fluorescence microscopy (MPFM) and the like, thereby attracting great interest of researchers.
However, since most of the existing organic materials have a small multiphoton absorption cross section, a short absorption wavelength and limited application prospects, finding multiphoton absorption materials with a large absorption cross section and a long wavelength has become a hot spot in the field of nonlinear optics, and therefore multiphoton complexes with various structures, unique properties and simple synthesis have attracted extensive attention of researchers.
The transition metal complex has good photophysical properties such as high quantum yield, large Stokes shift, narrow emission peak, long luminescence life and the like (Angew. chem. int. Ed.,2020,59, 15987-. The multiphoton optically active complex material is designed and synthesized simply and effectively by changing the structure of the ligand to change the photophysical and other properties of the complex.
Based on the consideration, the terpyridine ligand with strong chelating capacity and Mn (II) form a complex, anilino and butyl introduced on the terpyridine ligand have rich electrons, and halogen is introduced to serve as auxiliary coordination atoms to form a D-A structure, so that the push-pull electron capacity is improved, and the multiphoton absorption property of the complex is enhanced.
The invention content is as follows:
the invention aims to solve the technical problem of providing a Mn (II) complex with AIE property and a living cell mitochondria targeting function, a preparation method and application thereof.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
mn (II) complex with AIE property and living cell mitochondria targeting function, FD-MnCl for short2The structural formula is as follows:
the preparation method of the Mn (II) complex with the AIE property and the function of targeting living cell mitochondria uses N, N-dibutylaniline as the initial raw material, and firstly uses the N, N-dibutylaniline and POCl3Reacting to obtain compound O, reacting with 2-acetylpyridine to obtain compound FD, and reacting with MnCl2Reacting to obtain complex FD-MnCl2。
The synthetic route is as follows:
the N, N-dibutylaniline is reacted with DMF and POCl3In a molar ratio of 1:3: 5.
The molar ratio of the compound O to the 2-acetylpyridine is 1: 2-5.
The compounds FD and MnCl2The molar ratio of (A) to (B) is 1: 1-3.
Use of the above mn (ii) complex having AIE properties and a function of targeting living cell mitochondria as a multiphoton absorbing material.
The 2,2:6', 2' -tripyridine is a compound containing polypyridine heterocycle, has stronger coordination capacity to transition metal ions Mn (II), and N, N-dibutyl group has strong electron-donating capacity, thereby being beneficial to intramolecular charge transfer and regulating the luminescence of the complex. The halogen atom is used as an auxiliary coordination atom, so that the electron pushing and pulling capability of the complex can be improved, and the nonlinear optical property can be enhanced (Dyes and pigments, 2015,117, 7-15). Moreover, the complex designed in the invention has the property of multi-photon Aggregation Induced Emission (AIE), and overcomes the fluorescence quenching (ACQ) caused by self-aggregation of most complexes at high concentration. Moreover, the complex can enter cells in a short time under the excitation wavelength of 800nm, penetrate cell membranes, display two-photon fluorescence in mitochondria, can be used for qualitatively tracking liver cancer cells, and the research result has great significance for life science research.
The invention has the beneficial effects that:
1. the novel terpyridine Mn (II) complex synthesized by the invention is a multi-photon absorption material with a cell developing function. The anilino and the butyl have abundant electrons, so that intramolecular charge transfer is facilitated, and the luminescence of the complex is adjusted. Halogen atoms are introduced, the electron push-pull capability is improved, and the nonlinear optical property is enhanced. Compared with other materials, the complex has the characteristics of larger three-photon absorption cross section, low excitation energy, long wavelength, strong penetrability, small light damage and the like, can be used for multi-photon biological imaging, and has obvious application value.
2. Study of the Complex FD-MnCl Using the open-cell Z-Scan method and fluorescence contrast2Multi-photon absorption properties of (a). FD-MnCl at 800nm excitation wavelength using an open-cell Z-scan method2The maximum two-photon absorption cross section of the optical film reaches 1970.63 GM; FD-MnCl at an excitation wavelength of 1450nm2The maximum three-photon absorption cross section of the material reaches 2.09 multiplied by 10-75cm6s2photon-2(ii) a FD-MnCl at an excitation wavelength of 700nm using fluorescence contrast2The maximum two-photon absorption cross section of the material reaches 121.63GM, and the material has FD-MnCl at the excitation wavelength of 1450nm2The maximum three-photon absorption cross section of the material reaches 2.07 multiplied by 10-81cm6s2photon-2。
3. Mn (II) Complex FD-MnCl of the present invention2Having multiphoton AIE properties, three in aggregatePhoton fluorescence is significantly enhanced. As the water content increased from 0% to 70%, the fluorescence intensity did not change and the emission position was at 525 nm. Solute molecules keep a monomolecular state and do not form polymerization, but the fluorescence intensity is obviously enhanced along with the continuous increase of water content, when H is2FD-MnCl at 1450nm excitation wavelength when O reaches 80%2Has a three-photon absorption cross section of 9.68X 10-80cm6s2photon-246 times the initial absorption cross section. This phenomenon is caused by FD-MnCl2The formation of nano-polymers in water results in a decrease in solubility, activating intramolecular rotation (RIR) limited processes.
4. Coordination compound FD-MnCl by using laser confocal microscope2Cell imaging studies were performed. FD-MnCl in a short time when 800nm is used as an excitation wavelength2Enters HepG2 cells (liver cancer cells) and has two-photon fluorescence signals, which indicates that the complex FD-MnCl2Has strong cell permeability. To confirm the complex FD-MnCl2Targeting the site of the cell using the commercial dye Mito tracker redTMThe result of the co-localization development showed FD-MnCl2And Mito tracker redTMThe coloring part and phenomenon of FD-MnCl are consistent2Mitochondria of living cells can be targeted. The results of this study indicate the potential of the complex for two-photon bio-imaging applications.
5. The manganese terpyridine complex has the advantages of easily available raw materials, low price, short synthetic route and mild synthetic conditions.
Description of the drawings:
in figure 1 is complex FD-MnCl2Crystal structure diagram.
FIG. 2 (a-f) is a graph of the study of complex FD-MnCl using open-cell Z-scan method and fluorescence contrast method2Two/three photon absorption spectra in DMSO solvent (c ═ 10)-3mol/L). Graph a FD-MnCl using an open-cell Z-scan method at an excitation wavelength of 800nm2Maximum two-photon absorption cross-sectional view of (a); panel b FD-MnCl using an open-cell Z-scan method at an excitation wavelength of 1450nm2Maximum three-photon absorption cross-sectional view; panel c fluorescence contrast method at 680-8FD-MnCl at 60nm excitation wavelength2The two-photon fluorescence spectrum of (1); d picture FD-MnCl using fluorescence contrast method with 680-860nm as excitation wavelength2A two-photon absorption cross-sectional view of (a); the e-diagram uses fluorescence contrast method, FD-MnCl at 1150-1550nm as the excitation wavelength2The three-photon fluorescence spectrum of (a); the f diagram uses fluorescence contrast method, uses 1150-1550nm as excitation wavelength, FD-MnCl2Three photon absorption cross section.
FIG. 3 (a-b) Complex FD-MnCl2In different proportions (0% -90%, 98%) of CH3OH/H2Single photon fluorescence spectroscopy in O-mixed solvents (c ═ 10)-5mol/L); (c) under the excitation wavelength of 800nm, the complex FD-MnCl2In 0% -90%, 98% CH3OH/H2Two-photon fluorescence spectrum in O (c ═ 10)-3mol/L). (d) Under the excitation wavelength of 800nm, the complex FD-MnCl2In 0% -90%, 98% CH3OH/H2A two-photon absorption cross-sectional view in a mixed solvent of O; (e) FD-MnCl at an excitation wavelength of 1450nm2In 0% -90%, 98% CH3OH/H2Three-photon fluorescence spectrum in O (c ═ 10)-3mol/L); (f) under the excitation wavelength of 1450nm, the complex FD-MnCl2In 0% -90%, 98% CH3OH/H2And a three-photon absorption cross-sectional view in a mixed solvent of O.
FIG. 4 shows a complex FD-MnCl2The two-photon fluorescence development image of (1) has an excitation wavelength of 800nm and a scale of 20 μm; wherein A is a two-photon development pattern when 800nm is used as the excitation wavelength and 450-490nm is used as the emission wavelength; b is Mito tracker red using 405nm as the excitation wavelength and 560-600nm as the emission wavelengthTMA single photon development pattern of (a); c is a single-double photon overlay; d is bright field cell visualization; all figures were obtained using Image J software.
The specific implementation mode is as follows:
in order to make the technical means, the original characteristics, the achieved purposes and the effects of the invention easy to understand, the invention is further explained by combining the specific embodiments and the drawings.
1. Preparation of Compound O
Ice salt bath conditionsNext, refined DMF (4.38g,0.06mol) was weighed in a 500mL round-bottomed flask, and POCl was added dropwise thereto using an isobaric dropping funnel3(15.30g,0.1mol), after the frozen salt is formed, weighing N, N-dibutylaniline (4.10g,0.02mol), dissolving with 50mL chloroform, pouring into the frozen salt, after the frozen salt is melted, refluxing at 65 ℃ for 6 h. After the reaction is completed, pouring the reactant into a large amount of ice water, adjusting the pH value to be neutral by using NaOH aqueous solution, extracting by using dichloromethane, and distilling off the solvent at normal pressure to obtain oily liquid. And (3) performing silica gel column chromatography on the crude product, eluting the crude product by using petroleum ether as a developing agent to obtain a first component, namely the required product, and distilling the developing agent to obtain light yellow oily liquid 3.0g with the yield of 64%.
2. Preparation of Compound FD
Weighing 2-acetylpyridine (3.03g,0.025mol) in a 500mL round-bottom flask, dissolving with an appropriate amount of ethanol, weighing potassium hydroxide (1.6g,0.04mol), dissolving with a small amount of water, adding into the system, weighing compound O (1.17g,0.005mol), dissolving with an appropriate amount of ethanol, adding into the system, stirring at normal temperature for 1h, dropwise adding 70mL of ammonia water by using a constant-pressure dropping funnel, refluxing at 80 ℃ for 6h, stopping heating (supplementing ammonia water once in the middle), removing part of solvent, and recrystallizing with ethanol to obtain a bright yellow solid 3.00g with a yield of 68%.1H NMR(400MHz,d6-acetone,ppm)δ8.76(dd,J＝62.4,45.6Hz,4H),8.08–7.90(m,2H),7.44(t,J＝25.5Hz,4H),7.27(t,J＝16.5Hz,1H),7.17–6.94(m,1H),6.69(t,J＝19.6Hz,2H),3.47–3.23(m,4H),1.58(t,J＝18.5Hz,4H),1.38(dt,J＝27.3,13.6Hz,4H),1.13–0.80(m,6H).13C NMR(100MHz,d6-acetone,ppm)δ154.19,151.80,148.26,139.25,128.79,124.05,119.73,111.53,53.49,30.07,21.77,13.79.MS(ESI-MS):calc:436.60,found:437.27([M]+H+)
3. Complex FD-MnCl2Preparation of
Manganese chloride (0.16g,1.0mmol) is weighed into a 100mL round-bottom flask, an appropriate amount of anhydrous acetonitrile is added to completely dissolve the manganese chloride, a solution of ligand FD (0.44g,1.0mmol) in acetonitrile (10Ml) is dropwise added under the condition of normal temperature, the reaction is stopped after stirring for 2h, and the manganese chloride is filtered to obtain an orange solid with a yield of 0.38 g: 76 percent.1H NMR(400MHz,d6-DMSO)δ8.75–8.53(m,6H),7.98(d,J＝2.4Hz,2H),7.49(s,2H),6.79(s,2H),5.63–5.05(m,3H),1.83–1.46(m,5H),1.35–1.19(m,6H),0.91(t,J＝7.4Hz,6H).13C NMR(100MHz,d6-DMSO)δ(ppm):161.14,152.17,151.35,149.58,138.96,138.24,135.23,129.40,128.74,122.89,118.57,117.71,53.72,31.34,21.26,14.26.FT-IR(KBr,cm-1):3908(m),3844(s),3768(m),3558(m),3431(s),2962(m),2886(m),2364(m),1583(s),1532(s),1469(s),1418(s),1360(s),1202(s),1017(s),795(s).
Analysis of the attached figures:
FIG. 1 shows a complex FD-MnCl2Crystal structure diagram, the exact structure of the molecule is proved. The hydrogen atoms and solvent molecules are deleted in order to clearly show the crystal structure. Complex FD-MnCl2The single crystal of (A) is obtained by a solvent evaporation method, and an appropriate amount of FD-MnCl is added2Dissolved in 10mL of dichloromethane, filtered into a 25mL conical flask, covered with 5mL of ethanol, and placed in a vibration-free dark environment to obtain orange-yellow prismatic crystals with a size of 0.30X 0.20mm after two weeks. In the complex FD-MnCl2In the crystal data of (2), the complex belongs to the P ī space group, triclinic system. N, N-butyl terpyridine is used as a main ligand to coordinate with central Mn, and two Cl ions are used as coordination atoms to coordinate with the central Mn. The coordinated ligand and the metal ion are positioned on the same plane, namely the part of N ^ N ^ N-Mn is positioned on the same plane.
Panel a of FIG. 2 uses the open-hole Z-scan method, FD-MnCl at an excitation wavelength of 800nm2The maximum two-photon absorption cross section of the optical film reaches 1970.63 GM; panel b FD-MnCl using an open-cell Z-scan method at an excitation wavelength of 1450nm2The maximum three-photon absorption cross section reaches 2.09 multiplied by 10-75cm6s2photon-2(ii) a The c diagram uses fluorescence contrast method, and uses 680-860nm as excitation wavelength, FD-MnCl2When 800nm is used as excitation wavelength, the two-photon fluorescence intensity of the two-photon fluorescence spectrum is strongest; d picture FD-MnCl using fluorescence contrast method with 680-860nm as excitation wavelength2The maximum two-photon absorption cross section of the optical film reaches 121.63 GM; the e-diagram uses fluorescence contrast method, FD-MnCl at 1150-1550nm as the excitation wavelength2Of three photonsFluorescence spectrum, when 1450nm is used as excitation wavelength, the three-photon fluorescence intensity is strongest; the f picture adopts fluorescence contrast method, and FD-MnCl takes 1500nm as excitation wavelength2The maximum three-photon absorption cross section reaches 2.55 multiplied by 10-81cm6s2photon-2。
4. AIE property test: configuring CH with different proportions3OH/H2O (water content from 0% to 90%, 98%). Measurement of Complex FD-MnCl2At different ratios of CH3OH/H2Single/multiphoton fluorescence spectrum in a mixed solvent of O.
FIG. 3 shows a complex FD-MnCl2At different ratios of CH3OH/H2O in a mixed solvent, and the multiphoton AIE properties thereof were investigated. From the a-b diagrams, it can be seen that2The O content is increased from 0% to 50%, the fluorescence intensity is not changed at 525nm, and when the water content is more than 50%, the fluorescence is enhanced, and 70% of the water content is reached, the complex FD-MnCl2The fluorescence intensity of (a) is maximal; c is the complex FD-MnCl at the excitation wavelength of 800nm2At different ratios of CH3OH/H2Two-photon fluorescence Spectroscopy in O-Mixed solvent when H2When the O content reaches 70%, the two-photon fluorescence intensity is maximum; d is a graph showing that the maximum two-photon absorption cross-section reached 67.77GM at an excitation wavelength of 800nm when the water composition reached 70% as calculated using fluorescence contrast; e diagram shows the complex FD-MnCl at the excitation wavelength of 1450nm2At different ratios of CH3OH/H2Three photon fluorescence Spectroscopy in O Mixed solvent when H2When the content of O reaches 80%, the three-photon fluorescence intensity is maximum; f illustrates that the maximum three-photon absorption cross section reaches 9.68 x 10 at 1450nm excitation wavelength when the water component reaches 80% as calculated using fluorescence contrast method- 80cm6s2photon-2cm6s2photon-246 times the initial absorption cross section.
5. Cell culture and staining: HepG2 cells and DMEM medium are adopted for 24h culture. Media was removed by three washes with PBS prior to staining. Add 200. mu.L PBS to the petri dish followed by 20. mu. LFD-MnCl2Anhydrous DMSO solution (1X 10)- 3mol/L). After incubation for 15min in the dark, the solution was aspirated by a pipette, washed three times with PBS solution, and subjected to two-photon fluorescence microscopy and imaging.
As can be seen from FIG. 4, FD-MnCl2As a two-photon fluorescent probe, when 800nm is used as excitation wavelength, the probe can penetrate through cell membranes and target HepG2 cell mitochondria, and the co-localization coefficient of the probe reaches 0.85.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (6)
1. A mn (ii) complex having AIE properties and a function of targeting mitochondria in living cells, characterized in that: FD-MnCl for short2The structural formula is as follows:
2. a method of preparing a mn (ii) complex having AIE properties and a function of targeting mitochondria in living cells according to claim 1, wherein: n, N-dibutylaniline is used as the initial raw material, and N, N-dibutylaniline and POCl are firstly used3Reacting to obtain compound O, reacting with 2-acetylpyridine to obtain compound FD, and reacting with MnCl2Reacting to obtain complex FD-MnCl2；
The synthetic route is as follows:
3. the method of claim 2 for preparing mn (ii) complexes with AIE properties and function to target living cells mitochondria, wherein: the N, N-dibutylaniline is reacted with DMF and POCl3In a molar ratio of 1:3: 5.
4. The method of claim 2 for preparing mn (ii) complexes with AIE properties and function to target living cells mitochondria, wherein: the molar ratio of the compound O to the 2-acetylpyridine is 1: 2-5.
5. The method of claim 2 for preparing mn (ii) complexes with AIE properties and function to target living cells mitochondria, wherein: the compounds FD and MnCl2The molar ratio of (A) to (B) is 1: 1-3.
6. Use of a mn (ii) complex having AIE properties and a function of targeting living cell mitochondria according to any one of claims 1 to 5 as a multiphoton absorbing material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110482983.7A CN113201018B (en) | 2021-04-30 | 2021-04-30 | Mn (II) complex with AIE property and targeted living cell mitochondrial function, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110482983.7A CN113201018B (en) | 2021-04-30 | 2021-04-30 | Mn (II) complex with AIE property and targeted living cell mitochondrial function, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113201018A true CN113201018A (en) | 2021-08-03 |
| CN113201018B CN113201018B (en) | 2023-06-27 |
Family
ID=77028202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110482983.7A Active CN113201018B (en) | 2021-04-30 | 2021-04-30 | Mn (II) complex with AIE property and targeted living cell mitochondrial function, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113201018B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101412737A (en) * | 2008-11-28 | 2009-04-22 | 江苏大学 | Anti-tumor bipyridine methyl substituted manganese amino acid complex, and preparation and application thereof |
| CN102924524A (en) * | 2012-10-29 | 2013-02-13 | 安徽大学 | Manganese complex two-photon absorption material with living cell developing function and synthesis method thereof |
| WO2015077306A1 (en) * | 2013-11-19 | 2015-05-28 | Momentive Performance Materials Inc. | Cobalt catalysts and their use for hydrosilylation and dehydrogenative silylation |
| CN108409757A (en) * | 2018-04-03 | 2018-08-17 | 阜阳师范学院 | A kind of Zn complex and its preparation method and application |
-
2021
- 2021-04-30 CN CN202110482983.7A patent/CN113201018B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101412737A (en) * | 2008-11-28 | 2009-04-22 | 江苏大学 | Anti-tumor bipyridine methyl substituted manganese amino acid complex, and preparation and application thereof |
| CN102924524A (en) * | 2012-10-29 | 2013-02-13 | 安徽大学 | Manganese complex two-photon absorption material with living cell developing function and synthesis method thereof |
| WO2015077306A1 (en) * | 2013-11-19 | 2015-05-28 | Momentive Performance Materials Inc. | Cobalt catalysts and their use for hydrosilylation and dehydrogenative silylation |
| CN108409757A (en) * | 2018-04-03 | 2018-08-17 | 阜阳师范学院 | A kind of Zn complex and its preparation method and application |
Non-Patent Citations (3)
Also Published As
| Publication number | Publication date |
|---|---|
| CN113201018B (en) | 2023-06-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107603269B (en) | Fluorescent dye based on naphthalimide, preparation method and application thereof | |
| Wang et al. | A novel triphenylamine-based bis-Schiff bases fluorophores with AIE-Activity as the hydrazine fluorescence turn-off probes and cell imaging in live cells | |
| US9315465B2 (en) | Photostable AIE luminogens for specific mitochondrial imaging and its method of manufacturing thereof | |
| Li et al. | A near-infrared fluorescent probe for Cu2+ in living cells based on coordination effect | |
| Liu et al. | A glycosylation strategy to develop a low toxic naphthalimide fluorescent probe for the detection of Fe 3+ in aqueous medium | |
| Baig et al. | Easy access to new anthracenyl π-conjugates: generation of distinct AIE-active materials | |
| Yang et al. | BODIPY derivatives bearing borneol moieties: Enhancing cell membrane permeability for living cell imaging | |
| Bai et al. | Construction of an NIR and lysosome-targeted quinoline-BODIPY photosensitizer and its application in photodynamic therapy for human gastric carcinoma cells | |
| Wang et al. | Precise design and synthesis of an AIE fluorophore with near-infrared emission for cellular bioimaging | |
| Qu et al. | Molecular rotor based on dipyridylphenylamine: Near-infrared enhancement emission from restriction of molecular rotation and applications in viscometer and bioprobe | |
| Kong et al. | A two-photon AIE fluorophore as a photosensitizer for highly efficient mitochondria-targeted photodynamic therapy | |
| WO2023092814A1 (en) | Amino-substituted chromenoquinoline type fluorescent marker, and preparation and use thereof | |
| Wang et al. | Aggregation-induced emission compounds based on 9, 10-diheteroarylanthracene and their applications in cell imaging | |
| CN103382189B (en) | One class cyanine compound, its preparation method and application | |
| CN105670608B (en) | High-selectivity fluorescent probe capable of detecting nickel ions in mitochondria of living cells and preparation method thereof | |
| Tan et al. | Accessing conjugated and twisted structures for efficient dual-state emission fluorophore and its sensitive lysosomal imaging | |
| Sheng et al. | Hybridization of triphenylamine to BODIPY dyes at the 3, 5, 8-positions: A facile strategy to construct near infra-red aggregation-induced emission luminogens with intramolecular charge transfer for cellular imaging | |
| Yang et al. | Novel flavonoid derivatives and their corresponding rare earth complexes: Synthesis and luminescent properties | |
| Shu et al. | Small molecules based benzothiazole-pyridinium salts with different anions: Two-photon fluorescence regulation and difference in cell imaging application | |
| CN111793371B (en) | 3, 5-asymmetrically modified BODIPY near-infrared fluorescent dye and preparation method thereof | |
| Xiao et al. | Novel triphenylamine-cored two-photon absorbing dyes for labeling of biomolecules | |
| CN113201018A (en) | Mn (II) complex with AIE property and living cell mitochondria targeting function and preparation method and application thereof | |
| Yang et al. | An AIE triggered fluorescence probe with three-photon absorption and its biological applications | |
| CN112047876B (en) | Red two-photon fluorescent AIE compound and synthesis and application thereof | |
| CN114133413A (en) | Benzothiazole-triphenylamine compound 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 |