CN106674221B - A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe - Google Patents
A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe Download PDFInfo
- Publication number
- CN106674221B CN106674221B CN201611228931.2A CN201611228931A CN106674221B CN 106674221 B CN106674221 B CN 106674221B CN 201611228931 A CN201611228931 A CN 201611228931A CN 106674221 B CN106674221 B CN 106674221B
- Authority
- CN
- China
- Prior art keywords
- preparation
- ruthenium complex
- organic ligand
- novel
- fpic
- 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.)
- Expired - Fee Related
Links
- 239000012327 Ruthenium complex Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000013110 organic ligand Substances 0.000 title claims abstract description 27
- 239000000523 sample Substances 0.000 title abstract description 12
- 239000003068 molecular probe Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 29
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 29
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 27
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 229910052707 ruthenium Inorganic materials 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 230000036571 hydration Effects 0.000 claims description 6
- 238000006703 hydration reaction Methods 0.000 claims description 6
- 230000001376 precipitating effect Effects 0.000 claims description 6
- 125000000129 anionic group Chemical group 0.000 claims description 5
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 125000002091 cationic group Chemical group 0.000 claims description 4
- 239000012266 salt solution Substances 0.000 claims description 4
- 229910001488 sodium perchlorate Inorganic materials 0.000 claims description 4
- PCOJVRLVOOUDIS-UHFFFAOYSA-N C(=O)O.FC=1C=C2C=CNC2=CC1 Chemical compound C(=O)O.FC=1C=C2C=CNC2=CC1 PCOJVRLVOOUDIS-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 229940041181 antineoplastic drug Drugs 0.000 claims 1
- 150000003233 pyrroles Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 238000012984 biological imaging Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 230000003287 optical effect Effects 0.000 abstract description 3
- 150000003303 ruthenium Chemical class 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000005281 excited state Effects 0.000 abstract description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- -1 Indole-2-carboxylic acid-1,10-phenanthrolin-5-ylamide Chemical compound 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- WTXBRZCVLDTWLP-UHFFFAOYSA-N 5-fluoro-1H-indole-2-carboxylic acid Chemical compound FC1=CC=C2NC(C(=O)O)=CC2=C1 WTXBRZCVLDTWLP-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 125000001814 trioxo-lambda(7)-chloranyloxy group Chemical group *OCl(=O)(=O)=O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium 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
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- 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
- C09K2211/185—Metal complexes of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention belongs to complex technology fields, and in particular to a kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe.The present invention provides a kind of novel organic ligands and preparation method thereof.The present invention also provides a kind of novel ruthenium complexes, including Ru [M2(fpic)]X2Compound represented and/or its hydrate, wherein fpic is above-mentioned novel organic ligand.The present invention also provides a kind of fluorescence probes and a kind of pharmaceutical composition.The novel ruthenium complex has preferable water solubility, and optical property is excellent, and lifetime of excited state is long, good biocompatibility, and synthesis step is simple, can be used as a kind of novel fluorescent molecular probe, applied to the biological imaging field in life science.
Description
Technical field
The invention belongs to complex technology fields, and in particular to a kind of organic ligand and preparation method thereof, New Ruthenium cooperation
Object and fluorescence probe.
Background technique
Fluorescence probe refer to those can selective binding certain analyte, the fluorescence spectrum of system occurs certain therewith
The molecule of variation.In molecular probe design, luminous letter is regulated and controled by the variation of chemical structure, environment and intermolecular interaction
Number, so that the detection played to measured object acts on.Re (I), Ru (II), Ir (III), Pt (II) complex are a kind of transition metal
Complex, it is this kind of since preferable application value is commonly used for the luminophore of molecular probe in terms of biological imaging for it
Fluorescence probe has low consumption, high sensitivity, responding range wide due to its special optical physics and photochemical properties
Advantage is widely used in each ambit.In recent years, the research and development about transition metal fluorescence probe is rapid, more
Kind fluorescence probe has been designed to synthesize and be applied in the fields such as DNA, protein, gas sensor.
However, the problem of existing generally existing fluorescent emission of the fluorescent molecular probe unstable service life is short and poorly water-soluble, no
The biological imaging that can be applied to well in biomedical research.Therefore, researching and developing a kind of novel fluorescence probe is this field
Technical staff's technical problem urgently to be resolved.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of novel fluorescence probes that fluorescent emission is stable.On realizing
Purpose is stated, the specific technical solution of the present invention is as follows:
The present invention provides a kind of novel organic ligands, have structure shown in general formula (I):
The present invention also provides a kind of preparation methods of novel organic ligand, comprising:
By 5- fluoro indole formic acid, thionyl chloride and 5- amino -1,10- Phen hybrid reaction in reaction dissolvent, obtain
To novel organic ligand described in claim 1.
Preferably, the reaction dissolvent is benzene or pyridine.
The present invention also provides a kind of novel ruthenium complexes, including shown in formula (II) compound represented and/or formula (II)
Compound hydrate,
Ru[M2(fpic)]X2 (Ⅱ)；
Wherein, 1 M, 10- Phen or 2,2'- bipyridyl；
X is inorganic salt anionic；The inorganic salt anionic is ClO4-, NO3- or Br-；
Fpic is organic ligand, and the organic ligand has the structure as shown in general formula (I):
Preferably, in the novel ruthenium complex, M 1, when 10- Phen, the molecular structural formula of cationic portion is such as
Shown in formula (III):
In the novel ruthenium complex, M 2, when 2'- bipyridyl, the molecular structural formula of cationic portion such as formula (IV) institute
Show:
The present invention also provides a kind of preparation methods of novel ruthenium complex, comprising:
The organic coordination compound and second of novel organic ligand, ruthenium prepared by above-mentioned novel organic ligand or above-mentioned preparation method
Alcohol mixing, reflux are cooled to room temperature, and inorganic salt solution is added after filtering, and precipitating is precipitated, obtains above-mentioned novel ruthenium complex.
Preferably, the organic coordination compound of the ruthenium is two (2,2'- bipyridyl)-two chloro- two hydration rutheniums or two (1,10- neighbours
Phenanthroline)-two chloro- two hydrations rutheniums.
Preferably, to flow back under a nitrogen atmosphere, the return time is 6h for the reflux.
Preferably, the inorganic salt solution is NaClO4Aqueous solution.
The present invention also provides a kind of fluorescent molecular probes, comprising: above-mentioned novel ruthenium complex and/or the New Ruthenium are matched
Close the novel ruthenium complex that the preparation method of object is prepared.
The present invention also provides a kind of pharmaceutical compositions, comprising: the novel ruthenium complex and/or the New Ruthenium are matched
Close the novel ruthenium complex that the preparation method of object is prepared.
It is anti-in preparation that the present invention also provides the organic ligand or the novel ruthenium complexes or described pharmaceutical composition
Application in cancer drug.
Compared with prior art, the invention has the following advantages:
The present invention provides a kind of new organic ligands, structure novel, and one kind can be synthesized newly by reacting with organic ruthenium complex
Type ruthenium complex structure novel；The ruthenium complex has preferable water solubility, and optical property is excellent, and lifetime of excited state is long, raw
Object compatibility is good, and synthesis step is simple, can be used as a kind of novel fluorescent molecular probe, applied to the fluorescence in life science
Bio-imaging field.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Fig. 1 is Ru [(phen)2(fpic)](ClO4)2·2H2The fluorescent strength determining result of O in water；
Fig. 2 is Ru [(bpy)2(fpic)](ClO4)2·2H2The fluorescent strength determining result of O in water；
Fig. 3 is Ru [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime measurement result of O in water；
Fig. 4 is Ru [(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime measurement result of O in water；
Fig. 5 is Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescent strength determining result of the O in acetonitrile；
Fig. 6 is Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescent strength determining result of the O in acetonitrile；
Fig. 7 is Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result of the O in acetonitrile；
Fig. 8 is Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result of the O in acetonitrile；
Fig. 9 is Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result after O and DNA combination；
Figure 10 is Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result after O and DNA combination.
Specific embodiment
The invention discloses a kind of organic ligand fpic, have structure shown in general formula (I):
The invention discloses a kind of novel ruthenium complex that can be used as fluorescent molecular probe, the novel ruthenium complex is Ru
[M2(fpic)]X2, wherein M 1,10- Phen or 2,2'- bipyridyl；X is not influence the water-soluble ion of complex, excellent
It is selected as NO3 2-, the inorganic salt anionic, more preferably ClO4- such as Br-.
Structural formula such as formula (I) compound represented is the major ligand fpic, 5-Fluoro-1H- of the novel ruthenium complex
Indole-2-carboxylic acid-1,10-phenanthrolin-5-ylamide (is translated into: the fluoro- 1- indoles -2- acetyl of 5-
Base -1,10- o-phenanthroline -5- amine), it is a kind of novel organic ligand；
The preparation method of fpic specifically: 5- fluoro indole formic acid is added in benzene or pyridine, thionyl chloride is slowly added dropwise,
It is heated to reflux, is concentrated into crystal precipitation, 5- amino -1,10- Phen is then added, precipitating is collected in stirring, dry.It is changed
Learn reaction equation are as follows:
Ligand fpic, the organic coordination compound of ruthenium and the mixing of reaction dissolvent ethyl alcohol, flow back 6h under a nitrogen atmosphere, is cooled to room
Temperature, filtering, is added NaClO in filtrate4Precipitating is precipitated in aqueous solution, filters, and washs, dry, obtains the ruthenium complex.
When the organic coordination compound of the ruthenium is two (1,10- Phen)-two chloro- two hydrations ruthenium, the New Ruthenium cooperation
Shown in the molecular structure of object such as formula (a):
The organic coordination compound of the ruthenium is two (2,2'- bipyridyl)-two chloro- two hydrations rutheniums, the novel ruthenium complex
Shown in molecular structure such as formula (b):
Novel ruthenium complex provided by the invention has preferable water solubility, stable fluorescent emission, higher fluorescence volume
Sub- efficiency can be used as a kind of novel long-life phosphors molecular probe, be applied to biological imaging technique, has and widely answer
Use prospect.It is the probe that can be used in living imaging, the offer measured matter of real-time in-situ by the novel ruthenium complex exploitation
Dynamic process in vivo will play good facilitation for the fluorescent molecule detection research in life science.
Technical solution of the present invention is clearly and completely described below in conjunction with the specific embodiment of the invention, it is clear that
Described embodiment is a part of the embodiment of the present invention, instead of all the embodiments.Those skilled in the art should manage
Solution, modifies to specific embodiments of the present invention or is replaced on an equal basis to some technical characteristics, without departing from the present invention
The spirit of technical solution should all cover in the scope of protection of the invention.
The synthesis of 1 organic ligand fpic of embodiment
5- fluoro indole -2- formic acid (1.27g, 9.0mmol) is added in benzene, is heated to reflux, thionyl chloride is slowly added dropwise,
And the suspension is heated to reflux min；Then, by mixture vacuum concentration until the precipitation of pistac crystal, obtains 5- fluorine Yin
Diindyl -2- acyl chlorides.By the benzole soln of 5- fluoro indole -2- acyl chlorides be added drop-wise to dropwise 5- amino -1,10- o-phenanthroline (1.9g,
In pyridine solution 9.0mmol), and gained mixture is stirred at room temperature overnight；It staticly settles, filters and collect precipitating,
Then it is crystallized in ethanol solution, obtains khaki solid, yield 2.918g, yield 91%.
Fpic-1H NMR (400MHz, DMSO, ppm): δ 12.04 (3H, s), 10.96 (3H, s), 9.25 (4H, d, J=
3.3Hz),9.22-9.14(3H,m),8.97-8.72(7H,m),8.35(3H,s),8.16-7.95(7H,m),7.62(3H,d,J
=1.5Hz), 7.57-7.40 (8H, m), 7.26 (1H, d, J=17.4Hz), 7.20-6.99 (4H, m), 5.37-2.06 (95H,
M), 2.50 (18H, d, J=1.6Hz), 2.35 (21H, dd, J=119.7,52.0Hz), 2.10-0.52 (3H, m).
2 complex Ru [(phen) of embodiment2(fpic)](ClO4)2·2H2The preparation of O
By the Ru (phen) of 0.568g (1mmo1)2Cl2·2H2O, the fpic of 0.356g (1mmo1) is added in three-necked flask,
Ethyl alcohol is added, resulting mixture is flowed back 6h under a nitrogen atmosphere, is cooled to room temperature, is filtered.It is added in filtrate
NaClO4, stand, filter, precipitating water, ether wash to be dried in vacuo afterwards for several times, obtains Orange red solid product, yield is
2.918g, yield 75%.
Ru[(phen)2(fpic)]-1H NMR (400MHz, DMSO, ppm): δ 11.98 (22H, d, J=18.2Hz),
10.95(20H,s),8.93-8.73(129H,m),8.62(23H,s),8.40(84H,s),8.23-8.00(126H,m),
7.99-7.70 (130H, m), 7.67-7.38 (79H, m), 7.28 (7H, s), 7.13 (28H, dtd, J=24.7,9.2,
2.5Hz), 3.35 (629H, s), 2.47 (303H, d, J=29.2Hz), 2.36-1.23 (33H, m), 1.61 (21H, d, J=
304.8Hz), 1.23 (11H, s), 1.00 (9H, d, J=118.3).
3 complex Ru [(bpy) of embodiment2(fpic)](ClO4)2·2H2The preparation of O
By the Ru (bpy) of 0.480g (1mmo1)2Cl2·2H2O, the fpic of 0.356g (1mmo1) is added in three-necked flask,
Ethyl alcohol is added, resulting mixture is flowed back 6h under a nitrogen atmosphere, is cooled to room temperature, is filtered.It is added in filtrate
NaClO4, stand, filter, precipitating water, ether wash to be dried in vacuo afterwards for several times, obtains Orange red solid product, yield is
2.918g, yield 78%.
Ru[(bpy)2(fpic)]-1H NMR(400MHz,DMSO,ppm):δ12.00(1H,s),10.94(1H,s),
8.93-8.68(7H,m),8.62(1H,s),8.30-8.01(7H,m),8.01-7.68(5H,m),7.68-7.50(8H,m),
7.39 (2H, dd, J=12.3,5.2Hz), 7.26-7.04 (1H, m), 3.36 (94H, s), 2.42 (13H, d, J=69.8Hz),
2.10-1.96(1H,m),1.23(1H,s)。
Embodiment 4
Compound concentration is the Ru [(phen) of 10umol/L respectively2(fpic)](ClO4)2·2H2O and Ru [(bpy)2
(fpic)](ClO4)2·2H2The aqueous solution of O measures its absorbance with ultraviolet-uisible spectrophotometer and draws absorption spectrum song
Line, using wavelength as excitation wavelength, is then surveyed using Fluorescence Spectrometer respectively to obtain the characteristic absorption peak wavelength of complex
Try the fluorescence intensity and fluorescence lifetime of two kinds of complexs.
As shown in Figures 1 to 4, both complexs issue strong fluorescence in water, and fluorescence intensity is respectively
3.87×106cps、2.26×106cps.Moreover, the fluorescence lifetime of both complexs all meets two fingers number when taking water as a solvent
Attenuation curve, wherein Ru [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 215.45ns, 590.76ns, Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 306.52ns, 544.82ns.
Embodiment 5
Using acetonitrile respectively compound concentration be 10umol/L Ru [(phen)2(fpic)](ClO4)2·2H2O and Ru
[(bpy)2(fpic)](ClO4)2·2H2The acetonitrile solution of O measures its absorbance with ultraviolet-uisible spectrophotometer and draws suction
The curve of spectrum is received, to obtain the characteristic absorption peak wavelength of complex, using wavelength as excitation wavelength, then uses fluorescence spectrum
Instrument tests the fluorescence intensity and fluorescence lifetime of two kinds of complexs respectively.
As shown in Fig. 5 to Fig. 8, both complexs issue strong fluorescence in acetonitrile, and fluorescence intensity is respectively
1.31×106cps、8.96×105cps.Moreover, the fluorescence lifetime of both complexs all meets two fingers when using acetonitrile as solvent
Number attenuation curve, wherein Ru [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 111.81ns, 301.71ns, Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 144.18ns, 224.07ns.
Embodiment 6
Prepare the buffer of Tris containing 5mM and 50mM NaCl (hydrochloric acid tune pH value to 7.0).Appropriate buffer solution is taken to be added
Appropriate DNA is made into 5mg/mL DNA mother liquor.
Appropriate buffer solution is taken to be made into the Ru [(phen) of 10umol/L2(fpic)](ClO4)2·2H2The solution of O is added dropwise
5mg/mL DNA mother liquor measures the fluorescence intensity of complex after DNA is added, and then continues to that DNA solution is added dropwise, until being added dropwise to
Fluorescence intensity is basically unchanged, and tests its fluorescence lifetime.Similarly, 10umol/L Ru [(phen) is tested2(fpic)](ClO4)2·
2H2The DNA titration curve and fluorescence lifetime of O.
As shown in Figure 9 and Figure 10, after combining DNA, the fluorescence lifetime of both complexs still maintains double exponential dampings
Mode.Wherein, Ru [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O increases to 519.23ns, 1552.49ns, says
Bright complex Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime after O combination DNA is 2-3 times before combining；Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O increases to 538.26ns, 1384.27ns, illustrates complex Ru
[(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime after O combination DNA is 1-2 times before combining.
After DNA effect, the fluorescence intensity of the two complexs is remarkably reinforced, with the increase of DNA concentration, two cooperations
The fluorescence of object gradually increases, complex Ru [(phen)2(fpic)](ClO4)2·2H2O is reached when being added dropwise to 440ul DNA mother liquor
To saturation, fluorescence intensity increases about 13.2%, complex Ru [(bpy)2(fpic)](ClO4)2·2H2O is being added dropwise to 380ul
Reaching saturation when DNA mother liquor, fluorescence intensity increases about 25.6%, after illustrating the two complexs in conjunction with DNA, fluorescence intensity
There is the enhancing of certain amplitude with fluorescence lifetime.
Claims (12)
1. a kind of organic ligand, which is characterized in that have the structure as shown in general formula (I):
2. a kind of preparation method of organic ligand characterized by comprising
By 5- fluoro indole formic acid, thionyl chloride and 5- amino -1,10- Phen hybrid reaction in reaction dissolvent, obtain as
Organic ligand described in claim 1.
3. preparation method according to claim 2, which is characterized in that the reaction dissolvent is benzene or pyridine.
4. a kind of ruthenium complex, which is characterized in that including formula (II) compound represented and/or formula (II) compound represented
Hydrate,
Ru[M2(fpic)]X2(Ⅱ)；
Wherein, 1 M, 10- Phen or 2,2'- bipyridyl；
X is inorganic salt anionic；The inorganic salt anionic is ClO4 -、NO3 -Or Br-；
Fpic is organic ligand, and the organic ligand has the structure as shown in general formula (I):
5. ruthenium complex according to claim 4, which is characterized in that in the ruthenium complex, M 1,10- Phen
When, shown in the molecular structural formula of cationic portion such as formula (III):
In the ruthenium complex, M 2, when 2'- bipyridyl, shown in the molecular structural formula of cationic portion such as formula (IV):
6. a kind of preparation method of ruthenium complex, comprising:
By preparation method described in organic ligand described in claim 1 or Claims 2 or 3 preparation organic ligand, ruthenium it is organic
Complex and ethyl alcohol mixing, reflux are cooled to room temperature, and inorganic salt solution is added after filtering, precipitating is precipitated, obtains claim 4
Or ruthenium complex described in 5.
7. preparation method according to claim 6, which is characterized in that the organic coordination compound of the ruthenium is two (2,2'- connection pyrroles
Pyridine)-two it is chloro- two hydration rutheniums or two (1,10- Phen)-two it is chloro- two hydration rutheniums.
8. according to right want 6 described in preparation method, which is characterized in that the reflux is flows back under a nitrogen atmosphere, described time
The stream time is 6h.
9. according to right want 6 described in preparation method, which is characterized in that the inorganic salt solution be NaClO4Aqueous solution.
10. a kind of fluorescent molecular probe characterized by comprising ruthenium complex described in claim 2 or 3 and/or right are wanted
The ruthenium complex for asking preparation method described in 5-9 any one to be prepared.
11. a kind of pharmaceutical composition characterized by comprising ruthenium complex described in claim 4 or 5 and/or claim
The ruthenium complex that preparation method described in 6 to 9 any one is prepared.
12. the organic ligand or power of the preparation of preparation method described in organic ligand as described in claim 1 or Claims 2 or 3
Benefit require 4 or 5 described in preparation method preparation described in ruthenium complex or claim 6-9 any one ruthenium complex or right
It is required that pharmaceutical composition described in 11 is preparing the application in anticancer drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611228931.2A CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611228931.2A CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106674221A CN106674221A (en) | 2017-05-17 |
| CN106674221B true CN106674221B (en) | 2018-12-18 |
Family
ID=58873009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611228931.2A Expired - Fee Related CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106674221B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111808096B (en) * | 2020-06-30 | 2022-10-21 | 广东工业大学 | Novel ligand for copper ion detection, preparation thereof, novel ruthenium complex and near-infrared long-life fluorescent probe |
| CN112707903A (en) * | 2020-12-29 | 2021-04-27 | 广东省科学院化工研究所 | Metal organic coordination compound and preparation method and application thereof |
| CN115806677B (en) * | 2022-11-15 | 2023-09-01 | 广东工业大学 | Ruthenium polymer with photo-thermal conversion performance and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701024B (en) * | 2009-10-30 | 2013-07-03 | 暨南大学 | Ruthenium complex, preparation method thereof and application thereof |
| CN103880890A (en) * | 2014-03-21 | 2014-06-25 | 同济大学 | Novel antitumor drug-ruthenium (Ru) (II) complex and preparation method thereof |
| CN105732723B (en) * | 2016-03-18 | 2018-08-28 | 同济大学 | A kind of ruthenium (II) multi-pyridine ligand and its preparation and application |
-
2016
- 2016-12-27 CN CN201611228931.2A patent/CN106674221B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| A novel anion receptor employing the pyrrole and amide moieties in the cooperative binding of anions;Jie Shao等;《J Incl Phenom Macrocycl Chem》;20080729;第62卷;第377-381页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106674221A (en) | 2017-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106674221B (en) | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe | |
| Shen et al. | A specific AIE and ESIPT fluorescent probe for peroxynitrite detection and imaging in living cells | |
| Xu et al. | Structures and Photophysical Properties of Homo-and Heteronuclear Lanthanide (III) Complexes with Bridging 2-Methyl-8-hydroxylquinoline (HMq) in the μ-Phenol Mode | |
| Zhang et al. | A highly selective bis (salamo)-based fluorescent sensor for two-pronged recognitions to Cu2+ and Arg | |
| Zhu et al. | Syntheses, structures, molecular and cationic recognitions and catalytic properties of two lanthanide coordination polymers based on a flexible tricarboxylate | |
| CN107987282B (en) | Water-stable lanthanide metal-organic framework material, preparation and application thereof | |
| CN108676554B (en) | Composite nano probe and preparation method and application thereof | |
| CN111929252B (en) | Method for specifically and invisibly identifying ATP (adenosine triphosphate) based on zinc complex circular polarization luminescence property | |
| Yang et al. | Synthesis of multi-emission MOF composites for multi-dimensional sensing application | |
| Jin et al. | Sonochemical effect on two new Ruthenium (II) complexes with ligand (E)-N-((6-bromopyridin-2-yl) methylene)-4-(methylthio) aniline precursors for synthesis of RuO2 nanoparticles | |
| US5958673A (en) | Fluorescent dye | |
| Li et al. | Naked-eye-based selective detection of pyrophosphate with a Zn 2+ complex in aqueous solution and electrospun nanofibers | |
| CN110776458B (en) | Fluorescent probe for detecting mitochondrial membrane potential and preparation method and application thereof | |
| JP6449489B2 (en) | Carboxylic ion cross-linked dinuclear iron sulfur cluster fluorescent probe, its production method and use thereof | |
| CN108276454A (en) | A kind of half sandwich complex of iridium with fluorescent characteristic two tooth cheland containing N^N and preparation method thereof, application | |
| CN112321841A (en) | Metal organic framework material based on biomolecules as well as preparation method and application thereof | |
| Fernández et al. | Easy Ketimine Formation Assisted by Heteropolynuclear Gold− Thallium Complexes | |
| Hau et al. | Assembly of organosilver (I) frameworks with terminal ethynide and ethenyl groups on separate pendent arms attached to an aromatic ring | |
| Gao et al. | Single crystal X-ray structure determination and enantiomeric recognition of chiral dinuclear europium (III) complexes towards BINOL | |
| CN110669350B (en) | Piperidyl BODIPY red-light fluorescent dye and preparation method and application thereof | |
| CN103254217B (en) | Metal complexes with durene-bridged bibenzimidazole as ligand, and preparation method and application thereof | |
| CN108503588B (en) | A kind of 3- methylpyrazole benzaldehyde contracting 4-AA schiff bases and preparation method thereof | |
| CN112521376A (en) | Chromene-pyridine derivative fluorescent probe, preparation method and application | |
| CN105884710B (en) | 1,3, 4-oxadiazole Cu based on calixarene2+Fluorescent probe and synthetic method thereof | |
| Li et al. | RETRACTED: Two mixed-ligand coordination polymers: selective detection of acac and treatment activity on peripheral artery disease by reducing the peptidyl arginine deiminase activity |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20181218 Termination date: 20211227 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |